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Baloxavir marboxil (baloxavir), approved as an anti-influenza drug in Japan in March 2018, can induce reduced therapeutic effectiveness due to PA protein substitutions. We assessed PA substitutions in clinical samples from influenza-infected children and adults pre- and post-baloxavir treatment, examining their impact on fever and symptom duration. During the 2022-2023 influenza season, the predominant circulating influenza subtype detected by cycling-probe RT-PCR was A(H3N2) (n = 234), with a minor circulation of A(H1N1)pdm09 (n = 10). Of the 234 influenza A(H3N2) viruses collected prior to baloxavir treatment, 2 (0.8%) viruses carry PA/I38T substitution. One virus was collected from a toddler and one from an adult, indicating the presence of viruses with reduced susceptibility to baloxavir, without prior exposure to the drug. Of the 54 paired influenza A(H3N2) viruses collected following baloxavir treatment, 8 (14.8%) viruses carried E23 K/G, or I38 M/T substitutions in PA. Variant calling through next-generation sequencing (NGS) showed varying proportions (6-100 %), a polymorphism and a mixture of PA/E23 K/G, and I38 M/T substitutions in the clinical samples. These eight viruses were obtained from children aged 7-14 years, with a median fever duration of 16.7 h and a median symptom duration of 93.7 h, which were similar to those of the wild type. However, the delayed viral clearance associated with the emergence of PA substitutions was observed. No substitutions conferring resistance to neuraminidase inhibitors were detected in 37 paired samples collected before and following oseltamivir treatment. These findings underscore the need for ongoing antiviral surveillance, informing public health strategies and clinical antiviral recommendations for seasonal influenza.
Assuntos
Substituição de Aminoácidos , Antivirais , Dibenzotiepinas , Farmacorresistência Viral , Vírus da Influenza A Subtipo H3N2 , Influenza Humana , Morfolinas , Piridonas , Triazinas , Proteínas Virais , Humanos , Dibenzotiepinas/uso terapêutico , Dibenzotiepinas/farmacologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/enzimologia , Triazinas/uso terapêutico , Triazinas/farmacologia , Japão , Antivirais/farmacologia , Antivirais/uso terapêutico , Morfolinas/uso terapêutico , Farmacorresistência Viral/genética , Criança , Adulto , Pré-Escolar , Adolescente , Proteínas Virais/genética , RNA Polimerase Dependente de RNA/genética , Feminino , Masculino , Tiepinas/uso terapêutico , Tiepinas/farmacologia , Lactente , Pessoa de Meia-Idade , Estações do Ano , Piridinas/uso terapêutico , Piridinas/farmacologia , Adulto Jovem , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , IdosoRESUMO
If some countries lead by example, standards may increasingly become normalized.
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Viés , COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/mortalidade , COVID-19/transmissãoRESUMO
The recurrent multiwave nature of coronavirus disease 2019 (COVID-19) necessitates updating its symptomatology. We characterize the effect of variants on symptom presentation, identify the symptoms predictive and protective of death, and quantify the effect of vaccination on symptom development. With the COVID-19 cases reported up to August 25, 2022 in Hong Kong, an iterative multitier text-matching algorithm was developed to identify symptoms from free text. Multivariate regression was used to measure associations between variants, symptom development, death, and vaccination status. A least absolute shrinkage and selection operator technique was used to identify a parsimonious set of symptoms jointly associated with death. Overall, 70.9% (54 450/76 762) of cases were symptomatic with 102 symptoms identified. Intrinsically, the wild-type and delta variant caused similar symptoms among unvaccinated symptomatic cases, whereas the wild-type and omicron BA.2 subvariant had heterogeneous patterns, with seven symptoms (fatigue, fever, chest pain, runny nose, sputum production, nausea/vomiting, and sore throat) more frequent in the BA.2 cohort. With ≥2 vaccine doses, BA.2 was more likely than delta to cause fever among symptomatic cases. Fever, blocked nose, pneumonia, and shortness of breath remained jointly predictive of death among unvaccinated symptomatic elderly in the wild-type-to-omicron transition. Number of vaccine doses required for reducing occurrence varied by symptoms. We substantiate that omicron has a different clinical presentation compared to previous variants. Syndromic surveillance can be bettered with reduced reliance on symptom-based case identification, increased weighing on symptoms predictive of death in outcome prediction, individual-based risk assessment in care homes, and incorporating free-text symptom reporting.
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COVID-19 , Vacinas , Idoso , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Hong Kong/epidemiologia , FebreRESUMO
Influenza is a highly contagious respiratory illness that commonly causes outbreaks among human communities. Details about the exact nature of the droplets produced by human respiratory activities such as breathing, and their potential to carry and transmit influenza A and B viruses is still not fully understood. The objective of our study was to characterize and quantify influenza viral shedding in exhaled aerosols from natural patient breath, and to determine their viral infectivity among participants in a university cohort in tropical Singapore. Using the Gesundheit-II exhaled breath sampling apparatus, samples of exhaled breath of two aerosol size fractions ("coarse" > 5 µm and "fine" ≤ 5 µm) were collected and analyzed from 31 study participants, i.e., 24 with influenza A (including H1N1 and H3N2 subtypes) and 7 with influenza B (including Victoria and Yamagata lineages). Influenza viral copy number was quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Infectivity of influenza virus in the fine particle fraction was determined by culturing in Madin-Darby canine kidney cells. Exhaled influenza virus RNA generation rates ranged from 9 to 1.67 × 105 and 10 to 1.24 × 104 influenza virus RNA copies per minute for the fine and coarse aerosol fractions, respectively. Compared to the coarse aerosol fractions, influenza A and B viruses were detected more frequently in the fine aerosol fractions that harbored 12-fold higher viral loads. Culturable virus was recovered from the fine aerosol fractions from 9 of the 31 subjects (29%). These findings constitute additional evidence to reiterate the important role of fine aerosols in influenza transmission and provide a baseline range of influenza virus RNA generation rates.
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Herpesvirus Cercopitecino 1 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Humanos , Animais , Cães , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Singapura , Aerossóis e Gotículas Respiratórios , RNA Viral/genéticaRESUMO
In June 2023, the UK began official hearings for its independent investigation into pandemic preparedness. Thus far, the inquiry has been told that planning has been wholly inadequate and that a future outbreak is inevitable. We present here four key problems that contributed to significant morbidity and mortality during the Coronavirus 2019 (COVID-19) pandemic over the past 3 years in the UK - and which will contribute to excess morbidity and mortality in the next outbreak. First, there was misunderstanding about what procedures were deemed as aerosol generating. Aerosol transmission has always been a component of respiratory viruses; however, no specific aerosol-generating procedures are required to transmit any respiratory pathogens over long distances. Second, policy-makers were too binary in their answers to the public in terms of questions about severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). This meant that, as evidence evolved and different conclusions were drawn, the public lost faith in both the UK Government and science. Third, public health guidance did not take into account that certain groups would be impacted differentially by public health guidelines and instead used a one-size-fits-all approach to non-pharmaceutical interventions. Finally, there was worsening of existing inequalities, especially in ethnic minority groups, that resulted in excessive numbers within certain cohorts becoming infected.
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COVID-19 , SARS-CoV-2 , Humanos , Pandemias/prevenção & controle , Etnicidade , Grupos Minoritários , Aerossóis e Gotículas RespiratóriosAssuntos
Máscaras , Mpox , Humanos , Estudos de Amostragem , Sistema Respiratório , Nasofaringe , Testes Respiratórios , ExpiraçãoRESUMO
The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of SARS-CoV-2 has given rise to multiple variants with varying pathogenicity and transmissibility, such as the Delta and Omicron variants. Individuals with advanced age or underlying comorbidities, including hypertension, diabetes and cardiovascular diseases, are at a higher risk of increased disease severity. Hence, this has resulted in an urgent need for the development of better therapeutic and preventive approaches. This review describes the origin and evolution of human coronaviruses, particularly SARS-CoV-2 and its variants as well as sub-variants. Risk factors that contribute to disease severity and the implications of co-infections are also considered. In addition, various antiviral strategies against COVID-19, including novel and repurposed antiviral drugs targeting viral and host proteins, as well as immunotherapeutic strategies, are discussed. We critically evaluate strategies of current and emerging vaccines against SARS-CoV-2 and their efficacy, including immune evasion by new variants and sub-variants. The impact of SARS-CoV-2 evolution on COVID-19 diagnostic testing is also examined. Collectively, global research and public health authorities, along with all sectors of society, need to better prepare against upcoming variants and future coronavirus outbreaks.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19 , Pandemias/prevenção & controle , Vacinação , Antivirais/uso terapêuticoAssuntos
Infecções por Citomegalovirus , Complicações Infecciosas na Gravidez , Humanos , Gravidez , Feminino , Líquido Amniótico , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Citomegalovirus/genética , Reação em Cadeia da Polimerase , Transmissão Vertical de Doenças InfecciosasRESUMO
PURPOSE OF REVIEW: The coronavirus disease 2019 pandemic has had a wide-ranging and profound impact on how we think about the transmission of respiratory viruses This review outlines the basis on which we should consider all respiratory viruses as aerosol-transmissible infections, in order to improve our control of these pathogens in both healthcare and community settings. RECENT FINDINGS: We present recent studies to support the aerosol transmission of severe acute respiratory syndrome coronavirus 2, and some older studies to demonstrate the aerosol transmissibility of other, more familiar seasonal respiratory viruses. SUMMARY: Current knowledge on how these respiratory viruses are transmitted, and the way we control their spread, is changing. We need to embrace these changes to improve the care of patients in hospitals and care homes including others who are vulnerable to severe disease in community settings.
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COVID-19 , SARS-CoV-2 , Humanos , Aerossóis e Gotículas Respiratórios , Pandemias/prevenção & controleAssuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Pandemias , Teste para COVID-19 , Técnicas de Laboratório ClínicoRESUMO
Monkeypox virus (MPXV) has spread globally. Emerging studies have now provided evidence regarding MPXV transmission, that can inform rational evidence-based policies and reduce misinformation on this topic. We aimed to review the evidence on transmission of the virus. Real-world studies have isolated viable viruses from high-touch surfaces for as long as 15 days. Strong evidence suggests that the current circulating monkeypox (mpox) has evolved from previous outbreaks outside of Africa, but it is yet unknown whether these mutations may lead to an inherently increased infectivity of the virus. Strong evidence also suggests that the main route of current MPXV transmission is sexual; through either close contact or directly, with detection of culturable virus in saliva, nasopharynx, and sperm for prolonged periods and the presence of rashes mainly in genital areas. The milder clinical presentations and the potential presence of presymptomatic transmission in the current circulating variant compared to previous clades, as well as the dominance of spread amongst men who have sex with men (MSMs) suggests that mpox has a developed distinct clinical phenotype that has increased its transmissibility. Increased public awareness of MPXV transmission modalities may lead to earlier detection of the spillover of new cases into other groups.
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Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Monkeypox virus , Homossexualidade Masculina , Sêmen , Surtos de DoençasRESUMO
Background: Rapid diagnostic and prognostic tests for coronavirus disease (COVID-19) are urgently required. We aimed to evaluate the diagnostic and prognostic ability of breath analysis using gas chromatography-ion mobility spectrometry (GC-IMS) in hospitalized patients with COVID-19. Methods: Between February and May 2021, we took 1 breath sample for analysis using GC-IMS from participants who were admitted to the hospital for COVID-19, participants who were admitted to the hospital for other respiratory infections, and symptom-free controls, at the University Hospitals of Leicester NHS Trust, United Kingdom. Demographic, clinical, and radiological data, including requirement for continuous positive airway pressure (CPAP) ventilation as a marker for severe disease in the COVID-19 group, were collected. Results: A total of 113 participants were recruited into the study. Seventy-two (64%) were diagnosed with COVID-19, 20 (18%) were diagnosed with another respiratory infection, and 21 (19%) were healthy controls. Differentiation between participants with COVID-19 and those with other respiratory tract infections with GC-IMS was highly accurate (sensitivity/specificity, 0.80/0.88; area under the receiver operating characteristics curve [AUROC], 0.85; 95% CI, 0.74-0.96). GC-IMS was also moderately accurate at identifying those who subsequently required CPAP (sensitivity/specificity, 0.62/0.80; AUROC, 0.70; 95% CI, 0.53-0.87). Conclusions: GC-IMS shows promise as both a diagnostic tool and a predictor of prognosis in hospitalized patients with COVID-19 and should be assessed further in larger studies.
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UK National Health Service (NHS) Clinical Virology Departments provide a repertoire of tests on clinical samples to detect the presence of viral genomic material or host immune responses to viral infection. In December 2019, a novel coronavirus (SARS-CoV-2) emerged which quickly developed into a global pandemic; NHS laboratories responded rapidly to upscale their testing capabilities. To date, there is little information on the impact of increased SARS-CoV-2 screening on non-SARS-CoV-2 testing within NHS laboratories. This report details the virology test requests received by the Leicester-based NHS Virology laboratory from January 2018 to May 2022. Data show that in spite of a dramatic increase in screening, along with multiple logistic and staffing issues, the Leicester Virology Department was mostly able to maintain the same level of service for non-respiratory virus testing while meeting the new increase in SARS-CoV-2 testing.