Exploring antiviral effect and mechanism of Jinye Baidu granules（JYBD）against influenza A virus through network pharmacology and in vitro and invivo experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinye Baidu granules (JYBD) have been used to treat acute respiratory tract infections and demonstrated clinical efficacy for the treatment of emerging or epidemic respiratory viruses such as SARS-CoV-2 and influenza virus. AIM OF THE STUDY: This study is to investigate the antiviral effect of JYBD against influenza A viruses (IAV) in vitro and in vivo and elucidate its underlying mechanism. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography connected with Orbitrap mass spectrometer (UHPLC-Orbitrap MS) was employed to describe the chemical profile of JYBD. The potential pathways and targets involved in JYBD against IAV infection were predicted by network pharmacology. The efficacy and mechanism of JYBD were validated through both in vivo and in vitro experiments. Moreover, combination therapy with JYBD and the classic anti-influenza drugs was also investigated. RESULTS: A total of 126 compounds were identified by UHPLC-Orbitrap MS, of which 9 compounds were unambiguously confirmed with reference standards. JYBD could significantly inhibit the replication of multiple strains of IAV, especially oseltamivir-resistant strains. The results of qRT-PCR and WB demonstrated that JYBD could inhibit the excessive induction of pro-inflammatory cytokines induced by IAV infection and regulate inflammatory response through inhibiting JAK/STAT, NF-κB and MAPK pathways. Moreover, both JYBD monotherapy or in combination with oseltamivir could alleviate IAV-induced severe lung injury in mice. CONCLUSIONS: JYBD could inhibit IAV replication and mitigate virus-induced excessive inflammatory response. Combinations of JYBD and neuraminidase inhibitors conferred synergistic suppression of IAV both in vitro and in vivo. It might provide a scientific basis for clinical applications of JYBD against influenza virus infected diseases.

Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Impact of the COVID-19 pandemic on the treatment of acute cholangitis caused by choledocholithiasis: A single-center retrospective study in Japan.

Objectives: This study aimed to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on the treatment of acute cholangitis caused by choledocholithiasis. Methods: The Japanese government declared a state of emergency in April 2020 due to the COVID-19 pandemic. We retrospectively reviewed the medical records of 309 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis caused by choledocholithiasis between April 2017 and December 2022. Results: Patients were categorized into a pregroup (n = 134) and a postgroup (n = 175), depending on whether they were diagnosed before or after the state of emergency declaration. The total number of ERCP cases and the number of ERCP cases with endoscopic stone removals increased after the state of emergency declaration. Compared with the pregroup, the numbers of patients with performance status of 0-1 and surgically altered anatomy increased, whereas the numbers of patients taking oral antiplatelets or anticoagulants and those with cerebrovascular disease decreased in the postgroup. The number of single-stage endoscopic stone removals increased and hospital stays were significantly shorter in the postgroup. No differences in adverse event rates were detected between the two groups. Conclusions: Although our hospital provides tertiary care, the number of patients with cholangitis in good general condition and no underlying disease increased after the state of emergency declaration. The COVID-19 pandemic resulted in an increase in the number of single-stage endoscopic treatments and shortened hospital stays for patients with acute cholangitis caused by choledocholithiasis. No safety issues with ERCP were detected, even during the pandemic.

Epidemiological Study in Antiviral Innate Immunity.

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.

Exploring the HONO source during the COVID-19 pandemic in a megacity in China.

HONO is a critical precursor of •OH, but its sources are controversial due to its complex formation mechanism. This study conducted comprehensive observations in Zhengzhou from April 26 to May 11, 2022. Low NOx concentrations were observed during the Covid epidemic period (EP) (10.4 ± 3.0 ppb), compared to the pre-epidemic period (PEP) (12.5 ± 3.8 ppb). The mean HONO concentration during EP (0.53 ± 0.34 ppb) was 0.09 ppb lower than that during PEP (0.62 ± 0.53 ppb). The decrease in HONO concentration during EP came mainly at night due to the reduction in the direct emission (Pemi) (0.03 ppb/hr), the homogeneous reaction between •OH and NO (POH+NO) (0.02 ppb/hr), and the heterogeneous conversion of NO2 on the ground (0.01 ppb/hr). Notably, there was no significant change in daytime HONO concentration. The daytime HONO budget indicated that the primary HONO sources during PEP were the nitrate photolysis (Pnitrate), followed by the POH+NO, Pemi, the photo-enhanced reaction of NO2 on the ground (Pground+hv) and aerosol surface (Paerosol+hv). The primary HONO sources were Pnitrate, POH+NO, Pemi, and Paerosol+hv during EP, respectively. The missing source has a high correlation with solar radiation, there might be other photo-related HONO sources or the contributions of photosensitized reactions were underestimated. In the extremely underestimated cases, HONO production rates from the Pnitrate, Pground+hv, and Paerosol+hv increased by 0.17, 0.10, and 0.10 ppb/hr during PEP, 0.23, 0.13, and 0.16 ppb/hr during EP, and Pnitrate was still the primary source during both PEP and EP.

Programa de controle do tabagismo em Mato Grosso do Sul: oferta, adesão e efetividade / Smoking control program in Mato Grosso do Sul: offer, adherence and effectiveness / Programa de control del tabaquismo en Mato Grosso do Sul: oferta, adherencia y efectividad

Objetivo: O estudo teve por objetivo avaliar o Programa Nacional de Controle do Tabagismo (PNCT) em Mato Grosso do Sul, taxas de cobertura, abandono, cessação, uso de medicamentos, rede de serviços de saúde e as razões pelas quais algumas Equipes de Saúde da Família de Campo Grande ainda não aderiram ao programa. Métodos: Trata-se de uma pesquisa descritiva, com abordagem quantitativa, baseada em dados primários e secundários sobre o PNCT em Mato Grosso do Sul. Os dados primários foram obtidos por meio de questionário aplicado aos profissionais das Equipes de Saúde da Família (ESF) de Campo Grande, sem oferta do programa e avaliados quanto à frequência e presença de correlação entre as variáveis analisadas utilizando V de Cramer e teste de χ2. Os dados secundários foram obtidos do consolidado do Instituto Nacional de Câncer José Alencar Gomes da Silva com os registros produzidos pelos serviços. Resultados: As taxas de adesão, efetividade e apoio farmacológico na capital e interior foram: 66,80 e 59,79%; 20,58 e 34,91%; 32,14 e 99,86%, respectivamente. A oferta do programa ocorreu em 49,37% municípios e 43,85% das Unidades Básicas de Saúde (UBS) estimadas. Houve correlações entre ser capacitado e implantar o programa; treinamento de ingresso e oferta na UBS. As dificuldades relatadas pelos profissionais foram a pandemia de COVID-19, a sobrecarga e/ou equipe pequena e/ou falta de tempo e a ausência de capacitação/treinamento. Conclusões: O PNCT em Mato Grosso do Sul apresenta baixa cobertura e oferta restrita na rede de saúde, além do desempenho mediano de assistência aos tabagistas. Evidencia-se a necessidade de investimento em capacitação/treinamento, prioritariamente para as ESF de Campo Grande, dando-lhes condições de responder às necessidades de promoção da saúde, reconhecendo o programa como de maior custo-efetividade.

Objective: The objective of this study was to evaluate the National Tobacco Control Program (PNCT) in Mato Grosso do Sul, coverage rates, dropout, cessation, use of medication, the health services network and the reasons why Family Health Teams in Campo Grande have not yet joined the program. Methods: This was a descriptive study with a quantitative approach, based on primary and secondary data on the PNCT in Mato Grosso do Sul. The primary data were obtained by means of a questionnaire administered to Family Health Teams (ESF) in Campo Grande, which did not offer the program and evaluated the frequency and presence of correlation between the variables analyzed using Cramer's V test and the χ2 test. The secondary data were obtained from the consolidated records of the José Alencar Gomes da Silva National Cancer Institute with the records produced by the services. Results: The rates of adherence, effectiveness and pharmacological support in the capital and interior were: 66.80 and 59.79%; 20.58 and 34.91%; and 32.14 and 99.86%, respectively. The program was offered in 49.37% of the municipalities and 43.85% of the Basic Health Units (UBS) estimated. There were correlations between being trained and implementing the program and entry training and provision in the UBS. The difficulties reported by professionals were the COVID-19 pandemic, overload and/or a small team and/or lack of time and the absence of training. Conclusions: The PNCT in Mato Grosso do Sul has low coverage and restricted supply in the health network, in addition to average performance in assisting smokers. There is a clear need to invest in capacitation/training, primarily for the ESF in Campo Grande, enabling them to respond to the needs of health promotion, recognizing the program as more cost-effective.

Objetivo: El objetivo de este estudio fue evaluar el Programa Nacional de Control del Tabaco (PNCT) en Mato Grosso do Sul, las tasas de cobertura, el abandono, la cesación, el uso de medicamentos, la red de servicios de salud y las razones por las que los Equipos de Salud de la Familia en Campo Grande aún no se han unido al programa. Métodos: Se trata de un estudio descriptivo con abordaje cuantitativo, basado en datos primarios y secundarios sobre el PNCT en Mato Grosso do Sul. Los datos primarios se obtuvieron por medio de un cuestionario aplicado a los Equipos de Salud de la Familia (ESF) de Campo Grande, que no ofrecían el programa y evaluaron la frecuencia y la presencia de correlación entre las variables analizadas utilizando la V de Cramer y la prueba de la χ2. Los datos secundarios se obtuvieron de los registros consolidados del Instituto Nacional del Cáncer José Alencar Gomes da Silva con los registros producidos por los servicios. Resultados: Las tasas de adherencia, eficacia y apoyo farmacológico en la capital y en el interior fueron: 66,80 y 59,79%; 20,58 y 34,91%; 32,14 y 99,86%, respectivamente. El programa fue ofrecido en el 49,37% de los municipios y en el 43,85% de las Unidades Básicas de Salud (UBS) estimadas. Hubo correlación entre estar capacitado e implementar el programa; capacitación de entrada y oferta en las UBS. Las dificultades relatadas por los profesionales fueron la pandemia del COVID-19, la sobrecarga y/o un equipo pequeño y/o la falta de tiempo y la ausencia de capacitación. Conclusiones: El PNCT en Mato Grosso do Sul tiene baja cobertura y oferta restringida en la red de salud, además de un desempeño medio en la asistencia a los fumadores. Hay una clara necesidad de invertir en la creación de capacidad / formación, principalmente para la ESF en Campo Grande, lo que les permite responder a las necesidades de promoción de la salud, reconociendo el programa como más rentable.

Prevalência de Influenza A, vírus sincicial respiratório eSARS-CoV-2 em pacientes com síndrome respiratóriaaguda grave em Passo Fundo, Rio Grande do Sul / Prevalence of Influenza A, respiratory syncytial virus andSARS-CoV-2 in patients with severe acute respiratorysyndrome in Passo Fundo, Rio Grande do Sul

A síndrome respiratória aguda grave (SRAG) é caracterizada por sintomas de febre alta, tosse e dispneia, e, na maioria dos casos, relacionada a uma quantidade reduzida de agentes infecciosos. O objetivo foi avaliar a prevalência dos vírus respiratórios Influenza A (FluA), vírus sincicial respiratório (RSV) e do novo coronavírus (SARS-CoV-2) em pacientes com internação hospitalar por SRAG. Estudo transversal, com pacientes em internação hospitalar com SRAG entre novembro de 2021 e maio de 2022. Dados sociodemográficos e clínicos e amostras da nasofaringe foram coletados/as, as quais foram submetidas à extração de RNA e testadas quanto à positividade para Influenza A, RSV e SARS-CoV-2 por meio da técnica de PCR em tempo real pelo método SYBR Green. Foram incluídos 42 pacientes, sendo 59,5% do sexo feminino, 57,1% idosos, 54,8% com ensino fundamental. A maior parte dos pacientes reportou hábito tabagista prévio ou atual (54,8%), não etilista (73,8%) e 83,3% deles apresentavam alguma comorbidade, sendo hipertensão arterial sistêmica e diabetes mellitus tipo 2 as mais prevalentes. Um total de 10,5% dos pacientes testou positivo para FluA, nenhuma amostra positiva para RSV e 76,3% positivos para SARS-CoV-2. Na população estudada, SRAG com agravo hospitalar foi observado em maior proporção, em mulheres, idosos e pessoas com comorbidades, embora sem significância estatística, sendo o novo coronavírus o agente etiológico mais relacionado, o que evidencia a patogenicidade desse agente e suas consequências ainda são evidentes após quase 2 anos de período pandêmico.

Severe acute respiratory syndrome (SARS) is characterized by symptoms of high fever, cough and dyspnea, and is in most cases related to a reduced amount of infectious agents. The objective was to assess the prevalence of respiratory viruses Influenza A (FluA), respiratory syncytial virus (RSV) and the new coronavirus (SARS-CoV-2) in patients hospitalized for SARS. Cross-sectional study, with patients hospitalized with SARS between November 2021 and May 2022. Sociodemographic and clinical data and nasopharyngeal samples were collected, which were subjected to RNA extraction and tested for positivity for Influenza A, RSV and SARS-CoV-2 using the real-time PCR technique using the SYBR Green method. 42 patients were included, 59.5% female, 57.1% elderly, 54.8% with primary education. Most patients reported previous or current smoking habits (54.8%), non-drinkers (73.8) and 83.3% of them had some comorbidity, with systemic arterial hypertension and type 2 diabetes mellitus being the most prevalent. A total of 10.5% of patients tested positive for FluA, no samples positive for RSV, and 76.3% positive for SARS-CoV-2. In the studied population, SARS with hospital injury was observed more frequently in women and the elderly, with associated comorbidities, with the new coronavirus being the most related etiological agent, which shows, although not statistically significant, that the pathogenicity of this agent and its consequences are still evident after almost 2 years of period pandemic.

Comparative analysis of the incidence of enteroparasitosis andthe COVID-19 pandemic profile in the city of Bananeiras - PB / Análise comparativa da incidência de enteroparasitoses e doperfil pandêmico da COVID-19 na cidade de Bananeiras - PB

Enteroparasitosis are diseases caused by parasitic agents present in the environment and in the gastrointestinal tract of living beings. In addition, they are still considered neglected diseases, but of great importance for public health, especially when they are related to secondary infections and currently their co-infection profile with COVID-19. The interaction of protozoa and/or helminths with the SARS-CoV-2 virus is timely and its signs and symptoms are confused with other pathogen relationships. In this way, this study aims to correlate the incidence of enteroparasitosis and COVID-19, in the pandemic period from 2020 to April 2022. This is a documentary and exploratory study of secondary data from laboratory tests of patients who were treated and diagnosed with COVID-19 and enteroparasitosis at Hospital Doutor Cloves Bezerra Cavalcante, Municipal Hospital of Bananeiras, Paraíba, Brazil. In the analysis of the database, a significant increase of approximately 48.85% in the incidence of COVID-19 cases from 2020 to 2021 stands out, remaining high until 2022. In contrast, cases of enteroparasites peaked at 48.74% in 2021, followed by an average reduction of 23.12%, with a deviation of 1.49%, in relation to the years 2020 and 2022. It was concluded that COVID-19 is predominantly associated with an increase in secondary infections, highlighting the crucial need to promote health education, improve basic sanitation and guarantee access to health services as essential components in combating the increase in parasitic infections, especially those related to viral pathologies.

As enteroparasitoses são enfermidades originadas por agentes parasitários presentes no meio ambiente e no trato gastrointestinal dos seres vivos. Ademais, ainda são consideradas doenças negligenciadas, porém de grande importância para a saúde pública, em especial, quando estão relacionadas com infecções secundárias e atualmente seu perfil de coinfecção com a COVID-19. A interação de protozoários e/ou helmintos com o vírus SARS-CoV-2 é oportuna e seus sinais e sintomas são confundidos com outras relações de patógenos. Desta maneira, este estudo visa correlacionar a incidência de enteroparasitoses e COVID-19, no período pandêmico de 2020 a abril de 2022. Trata--se de uma pesquisa documental e exploratória, de dados secundários dos exames laboratoriais de pacientes que foram atendidos e diagnosticados com COVID-19 e enteroparasitoses no Hospital Doutor Cloves Bezerra Cavalcante, Hospital Municipal de Bananeiras, Paraíba, Brasil. Na análise da base de dados, destaca-se um aumento significativo de aproximadamente 48,85% na incidência de casos de COVID-19 de 2020 a 2021, mantendo-se elevado até 2022. Em contraste, os casos de enteroparasitas atingiram um pico de 48,74% em 2021, seguido por uma redução média de 23,12%, com um desvio de 1,49%, em relação aos anos de 2020 e 2022. Conclui-se que a COVID-19 está predominantemente associada ao aumento de infecções secundárias, destacando a necessidade crucial de promover a educação em saúde, melhorar o saneamento básico e garantir o acesso aos serviços de saúde como componentes essenciais no combate ao aumento de infecções parasitárias, especialmente aquelas relacionadas a patologias virais.

Serious adverse events reporting in recent randomised clinical trials in intensive care medicine - A methodological study protocol.

BACKGROUND: Serious adverse events (SAEs) are common in intensive care unit (ICU) patients. Reporting of SAEs in randomised clinical trials (RCTs) varies why underreporting is likely. We aim to describe the reporting of SAEs from 2020 onwards and to illustrate the recent reporting of SAEs published in major medical journals. METHODS: We will conduct a methodological study assessing pharmacological interventions in RCTs including adult ICU patients. We will search 10 general medical and critical care journals in PubMed. We will include all RCTs published from 2020 onwards. The primary research question is how many RCTs report SAEs in the primary publication. Secondary research questions include how SAEs are reported in the primary publication either as (1) proportion of patients experiencing one or more SAE, (2) all single events occurred, or (3) both strategies combined. We will assess the association between the proportion of patients with reported SAEs and the following trial characteristics: multicentred versus single-centre RCTs, industry-sponsored versus academic-sponsored, published trial protocol versus unpublished work, blinding, trials sample size, and RCTs focusing on COVID-19 patients versus other populations. DISCUSSION: The outlined methodological study will provide important information on the reporting of SAEs in recent drug trials in adult ICU patients.

Prolonged Grief, Posttraumatic Stress and Depression Symptoms Before and After COVID-19 in Brazil.

This study aims to explore the differences in prolonged grief (PDG), posttraumatic stress (PTSD), and depression symptoms (MDD) following the loss of a loved one before and after the COVID-19 pandemic. Using a cross-sectional design, 888 bereaved individuals were classified on different groups according to the cause of death. Results indicate that participants who experienced a loss during the pandemic, regardless of the cause, presented higher levels of prolonged grief, posttraumatic stress and depression when compared to those who lost a loved one before the pandemic. This study sheds light on the environmental influences (ex: the COVID-19 pandemic) on the grieving process, emphasizing the need to take the context into account when tailoring interventions in bereavement and mental health care.

The Incidence of Extreme Serum Prostate Specific Antigen Levels During the COVID-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic resulted in decreased prostate specific antigen (PSA) testing for prostate cancer screening and its impact remains uncharacterized. Our objective was to compare incident PSA testing rates, PSA levels, and prostate cancer treatment rates before and during the pandemic after the state of emergency (SoE) was declared. MATERIALS AND METHODS: This was a population-based, retrospective cohort study among men 50-80 years of age in Ontario, Canada undergoing incident PSA testing from November 23, 2018 to July 9, 2021. Working backwards and forwards from the date of the province-wide SoE (March 17, 2020), 30-day time periods were constructed during which incident PSA testing rates were measured. Our primary outcome was the rate of incident PSA testing. Secondary endpoints included comparison of incident PSA levels and prostate cancer treatment rates. RESULTS: We identified 835,402 men who underwent incident PSA testing. There was a 20% decrease in PSA testing after the SoE (RR = 0.80,95% CI: 0.800.81, P < .001). There was a higher proportion of extreme PSA levels after the SoE with a higher proportion of patients with a PSA >20 ng/mL (rate ratio = 1.63,95% CI: 1.54-1.73, P < .0001) and >100 ng/mL (rate ratio = 1.98,95% CI: 1.77-2.20, P < .0001). This effect was highest for those aged 50-59 years. More patients required active treatment (5,201,59.5% prior to the pandemic vs. 5,072,64.2%, P < .001 after the SoE declaration). CONCLUSIONS: The COVID-19 SoE resulted in patients experiencing a 2-fold increase in the risk of having an extreme PSA level and higher odds of treatment. Future studies are needed to assess the impact on the rates of advanced prostate cancer and cancer-specific mortality.

Responding to Domestic Violence and Abuse during COVID-19 through Remote Interventions: An Evaluation of the Identification and Referral to Improve Safety (IRIS) Service.

Aim: To explore the perspectives of patients/service users receiving specialist domestic violence and abuse (DVA) support from the Identification and Referral to Improve Safety (IRIS) service during the coronavirus disease 2019 (COVID-19) pandemic. Design: A qualitative approach was used to conduct this study. Methods: Thematic analysis of data collected via in-depth individual interviews with 11 patients/service users who received DVA support following their disclosure of abuse to a health-care professional in general practice (GP) and subsequent referral to the IRIS service. Findings: Six themes were identified-experience of DVA during COVID-19; awareness of the IRIS service; pathway to care; accessibility, safety, and remote consultations; adequacy of telephone support; and impact of IRIS support. Participants reported feeling supported by the GP team and the DVA specialists from the IRIS service. Conclusion: The pandemic had a significant impact on health care and specialist DVA service providers. The swift shift to remote consultations proved to be an effective way to identify DVA, determine the support needs of those experiencing DVA from their own perspective, and make appropriate referrals for specialist support. Further research is needed to understand the views of health-care professionals and those working in the IRIS service to explore factors affecting their ability to provide remote services. The study highlighted the need for health-care professionals other than doctors (including nurses, midwives, and others) to build knowledge, confidence, and competence in asking about DVA.

Real-world performance of a single-use, analyser-free, molecular point-of-care test for COVID-19 used in the emergency department: Results of a prospective trial (ED-POC).

BACKGROUND: A novel single-use, analyser-free, molecular point-of-care test for SARS-CoV-2 (Veros COVID-19 test, Sherlock Biosciences) could reduce time to results and improve patient care and flow in the emergency department (ED), but its performance in this setting is unknown. METHODS: Adults aged ≥18 years presenting to Southampton General Hospital (UK) with suspected COVID-19 were tested with the Veros COVID-19 test in addition to standard of care near-patient PCR. Measures of diagnostic accuracy were calculated for the Veros COVID-19 test stratified by Ct value. Discrepant results underwent viral culture. FINDINGS: Between Jan 16 and May 2, 2023, 400 patients were enrolled with a median (IQR) age of 60 (34-77) and 141 (35·3%) were SARS-CoV-2 positive by PCR. The Veros test gave valid results on the first test in 384 (96·0%), and sensitivity and specificity were 127/141 (90·1%, 95%CI 83·9-94·5) and 258/259 (99·6%, 95%CI 97·9-100) overall. For those with high or moderate viral load (Ct ≤30), sensitivity was 125/129 (96·9%, 95%CI 92·3-99·2). One (7·1%) of 14 PCR positive/Veros test negative samples was culture positive. Median (IQR) time from sample collection to result was 19 (18-20) mins with the Veros test versus 73 (59-92) mins with PCR (p < 0·0001). INTERPRETATION: The Veros COVID-19 test generated results in near real-time, around 1 h sooner than rapid, near-patient, analyser-based PCR, and accuracy was excellent for samples with moderate and high viral loads. The Veros test represents a step-change in molecular diagnostics for infection and could significantly reduce time to results and improve patient management in EDs and other settings.

Dimensionality reduction distills complex evolutionary relationships in seasonal influenza and SARS-CoV-2.

Public health researchers and practitioners commonly infer phylogenies from viral genome sequences to understand transmission dynamics and identify clusters of genetically-related samples. However, viruses that reassort or recombine violate phylogenetic assumptions and require more sophisticated methods. Even when phylogenies are appropriate, they can be unnecessary or difficult to interpret without specialty knowledge. For example, pairwise distances between sequences can be enough to identify clusters of related samples or assign new samples to existing phylogenetic clusters. In this work, we tested whether dimensionality reduction methods could capture known genetic groups within two human pathogenic viruses that cause substantial human morbidity and mortality and frequently reassort or recombine, respectively: seasonal influenza A/H3N2 and SARS-CoV-2. We applied principal component analysis (PCA), multidimensional scaling (MDS), t-distributed stochastic neighbor embedding (t-SNE), and uniform manifold approximation and projection (UMAP) to sequences with well-defined phylogenetic clades and either reassortment (H3N2) or recombination (SARS-CoV-2). For each low-dimensional embedding of sequences, we calculated the correlation between pairwise genetic and Euclidean distances in the embedding and applied a hierarchical clustering method to identify clusters in the embedding. We measured the accuracy of clusters compared to previously defined phylogenetic clades, reassortment clusters, or recombinant lineages. We found that MDS embeddings accurately represented pairwise genetic distances including the intermediate placement of recombinant SARS-CoV-2 lineages between parental lineages. Clusters from t-SNE embeddings accurately recapitulated known phylogenetic clades, H3N2 reassortment groups, and SARS-CoV-2 recombinant lineages. We show that simple statistical methods without a biological model can accurately represent known genetic relationships for relevant human pathogenic viruses. Our open source implementation of these methods for analysis of viral genome sequences can be easily applied when phylogenetic methods are either unnecessary or inappropriate.

SUB-immunogold-SEM reveals nanoscale distribution of submembranous epitopes.

Electron microscopy paired with immunogold labeling is the most precise tool for protein localization. However, these methods are either cumbersome, resulting in small sample numbers and restricted quantification, or limited to identifying protein epitopes external to the membrane. Here, we introduce SUB-immunogold-SEM, a scanning electron microscopy technique that detects intracellular protein epitopes proximal to the membrane. We identify four critical sample preparation factors contributing to the method's sensitivity. We validate its efficacy through precise localization and high-powered quantification of cytoskeletal and transmembrane protein distribution. We evaluate the capabilities of SUB-immunogold-SEM on cells with highly differentiated apical surfaces: (i) auditory hair cells, revealing the presence of nanoscale MYO15A-L rings at the tip of stereocilia; and (ii) respiratory multiciliate cells, mapping the distribution of the SARS-CoV-2 receptor ACE2 along the motile cilia. SUB-immunogold-SEM extends the application of SEM-based nanoscale protein localization to the detection of intracellular epitopes on the exposed surfaces of any cell.

Associations of demographic, health, and risk-taking behaviors with tattooing in a population-based cross-sectional study of ~18,000 US adults.

Background: Little is known about current characteristics of individuals with tattoos. We quantified the prevalence of tattooing and associations of demographic, health, and risk-behavior factors with tattooing. Methods: We computed adjusted prevalence ratios (PR) of tattooing in a population-based analysis of > 18,000 Utah adults from the 2020-2021 Behavioral Risk Factor Surveillance System survey. Results: The prevalence of tattooing was 26% among women and 22% among men, with the highest prevalence among women ages 25-29 (45%). Tattoo prevalence was higher among younger individuals, individuals with a lower education level, and those without religious affiliation. Tattoo prevalence was higher among indviduals with current tobacco (women: PR = 2.89 [95% confidence interval (CI): 2.60, 3.20]; men: 3.39 [2.98, 3.86]), e-cigarette (women: 2.44 [2.21, 2.69]; men: 2.64 [2.37, 2.94]), and heavy alcohol use (women: 2.16 [1.93, 2.43]; men: 1.89 [1.63, 2.19]). Tattoo prevalence was lower among individuals receiving a flu (women: 0.84 [0.76, 0.92]; men: 0.75 [0.67, 0.84]) or COVID-19 vaccine (women: 0.65 [0.54, 0.79]; men: 0.75 [0.61, 0.92]). Conclusions: Several risk-taking behaviors were associated with tattooing. Tattoo studios/conventions may present opportunities for partnership with tobacco cessation, alcohol reduction, and vaccination public health initiatives.

Self-rated health of Latino day laborers during the COVID-19 pandemic: a cross-sectional study.

Background: This study assesses the relationship between trust in sources of information in regard to the Coronavirus Disease 2019 (COVID-19) pandemic and self-rated health (SRH) in a sample of Latino Day Laborers (LDLs) and explores whether these associations were mediated by mental health measures. Methods: A rapid needs assessment survey was conducted with 300 LDLs, recruited at randomly selected hiring locations in Houston, Texas, during November and December 2021. Two measures of trust were developed, and SRH was measured by a single item. Depression, anxiety, and stress were measured by previously validated scales. We applied the product of coefficients approach to assess our mediation model. Using Hayes' PROCESS version 4.2 in SPSS, linear regression models were generated simultaneously to assess the total effect of trust on SRH, effect of trust on the mental health mediator, and effect of the mediator on SRH, controlling for trust. Demographic characteristics were entered as covariates. Results: Greater trust in formal sources of information (such as Spanish-speaking television networks) as well as greater levels of anxiety and depression were associated with lower SRH. There were no significant associations between formal trust and mental health measures. As such, the association between formal trust and decreased SRH was not mediated by mental health. Trust in informal sources of information (conversations with friends, family, and coworkers) was not significantly associated with SRH or mental health. Higher levels of depression and anxiety, however, were associated with lower SRH. Conclusions: LDLs' perception of their health was inversely associated with their level of trust in formal sources of information and with greater levels of depression and anxiety. Nevertheless, these pathways were independent of each other. The results indicate the direct impact of COVID-19 public information on subjective well-being, a relationship that merits further exploration.

Vaccination strategies for patients under monoclonal antibody and other biological treatments: an updated comprehensive review based on EMA authorizations to January 2024.

INTRODUCTION: Monoclonal antibodies (mAbs) and other biological agents are being increasingly approved in the last years with very different indications. Their highly heterogeneous immunosuppressive effects, mechanisms of action and pharmacokinetics require comprehensive individualized vaccination schedules. AREAS COVERED: Vaccination for immunocompromised patients. Prevention and treatment with mAbs and other biological therapies. EXPERT OPINION: Current recommendations on vaccine schedules for patients under mAbs or other biological treatments are based on expert opinions and are not individualized according to each vaccine and treatment. No studies are focusing on the high heterogeneity of these agents, that are exponentially developed and used for many different indications. Recent paradigm changes in vaccine development (boosted by the COVID-19 pandemic) and in the mAbs use for prophylactic purposes (changing 'vaccination' by 'immunization' schedules) has been witnessed in the last years. We aimed at collecting all mAbs used for treatment or prevention, approved as of 1 January 2024, by the EMA. Based on available data on mAbs and vaccines, we propose a comprehensive guide for personalizing vaccination. Recent vaccine developments and current population strategies (e.g. zoster vaccination or prophylactic nirsevimab) are discussed. This review aims to be a practical guideline for professionals working in vaccine consultations for immunosuppressed patients.

Symptom burden, coagulopathy and heart disease after acute SARS-CoV-2 infection in primary practice.

SETANTA (Study of HEarT DiseAse and ImmuNiTy After COVID-19 in Ireland) study aimed to investigate symptom burden and incidence of cardiac abnormalities after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 and to correlate these results with biomarkers of immunological response and coagulation. SETANTA was a prospective, single-arm observational cross-sectional study condcuted in a primary practice setting, and prospectively registered with ClinicalTrials.gov (identifier: NCT04823182). Patients with recent COVID-19 infection (≥ 6 weeks and ≤ 12 months) were prospectively enrolled. Primary outcomes of interest were markers of cardiac injury detected by cardiac magnetic resonance imaging (CMR), which included left ventricular ejection fraction, late gadolinium enhancement and pericardial abnormalities, as well as relevant biomarkers testing immunological response and coagulopathy. 100 patients (n = 129 approached) were included, amongst which 64% were female. Mean age of the total cohort was 45.2 years. The median (interquartile range) time interval between COVID-19 infection and enrolment was 189 [125, 246] days. 83% of participants had at least one persistent symptom, while 96% had positive serology for prior SARS-CoV-2 infection. Late gadolinium enhancement, pericardial effusion, was present in 2.2% and 8.3% respectively, while left ventricular ejection fraction was below the normal reference limit in 17.4% of patients. Von Willebrand factor antigen was elevated in 32.7% of patients and Fibrinogen and D-Dimer levels were found to be elevated in 10.2% and 11.1% of patients, respectively. In a cohort of primary practice patients recently recovered from SARS-CoV-2 infection, prevalence of persistent symptoms and markers of abnormal coagulation were high, despite a lower frequency of abnormalities on CMR compared with prior reports of patients assessed in a hospital setting.Trial Registration: Clinicaltrials.gov, NCT04823182 (prospectively registered on 30th March 2021).

Astodrimer sodium nasal spray forms a barrier to SARS-CoV-2 in vitro and preserves normal mucociliary function in human nasal epithelium.

COVID-19 remains a severe condition for many including immunocompromised individuals. There remains a need for effective measures against this and other respiratory infections, which transmit via virus-laden droplets that reach the nasal or oral mucosae. Nasal sprays offer potential protection against viruses. Such formulations should preserve normal nasal mucociliary function. The antiviral barrier efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were evaluated and compared with other available nasal sprays-low pH hydroxypropyl methylcellulose (HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). Assays simulated clinical conditions. Antiviral barrier function and cell viability were assessed in airway cell monolayers, while a model of fully differentiated human nasal epithelium (MucilAir™) was utilized to evaluate tissue integrity, cytotoxicity, cilia beating frequency, and mucociliary clearance. AS-NS reduced infectious virus in cell monolayers and demonstrated a benign cytotoxicity profile. In human nasal epithelium ex vivo, AS-NS had no impact on mucociliary function (cilia beating nor mucociliary clearance). Carr-NS, HPMC-NS, NO-NS and PI-NS demonstrated limited antiviral effects, while HPMC-NS caused inhibition of mucociliary function. Astodrimer sodium nasal spray demonstrates an acceptable nonclinical efficacy and safety profile as a barrier nasal spray against respiratory viral infection in the nasal cavity.