RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

Asunto(s)

Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Macrófagos , SARS-CoV-2 , Replicación Viral , Animales , Ratones , Células RAW 264.7 , Replicación Viral/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/virología , SARS-CoV-2/efectos de los fármacos , Antivirales/farmacología , Ratones Transgénicos , Pogostemon/química , Citocinas/metabolismo , Apoptosis/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/virología , Pulmón/patología , Glucósidos/farmacología , Glucósidos/aislamiento & purificación , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/uso terapéutico , Enzima Convertidora de Angiotensina 2/metabolismo , Antiinflamatorios/farmacología , Masculino , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Humanos

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. AIM OF THE STUDY: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. MATERIALS AND METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 µg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.

Asunto(s)

Antivirales , Medicamentos Herbarios Chinos , Aceites Volátiles , Infecciones por Orthomyxoviridae , Animales , Aceites Volátiles/farmacología , Medicamentos Herbarios Chinos/farmacología , Ratones , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Antivirales/farmacología , Ratones Endogámicos BALB C , Neumonía Viral/tratamiento farmacológico , Masculino , Células de Riñón Canino Madin Darby , Perros , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/virología , Pulmón/metabolismo , Humanos , Femenino , Neumonía/tratamiento farmacológico , Neumonía/virología , Neumonía/metabolismo

RESUMEN

Importance: Colchicine has many drug-drug interactions with commonly prescribed medications. Only pharmacokinetic studies have provided data on colchicine drug-drug interactions. Objective: To evaluate the clinical tolerability of colchicine according to the presence or absence of a drug-drug interaction. Design, Setting, and Participants: A secondary analysis of the COLCORONA trial was performed. The COLCORONA trial was a randomized, double-blind, placebo-controlled trial conducted in Brazil, Canada, Greece, South Africa, Spain, and the US between March 23, 2020, and January 20, 2021. The COLCORONA trial included ambulatory patients with COVID-19 with at least 1 high-risk characteristic and compared the effects of colchicine (0.5 mg twice daily for 3 days, then 0.5 mg daily thereafter) with placebo for 27 days. Data analysis was performed from February 24, 2023, to June 20, 2024. Exposure: In this secondary analysis, baseline medications that had interactions with colchicine were identified using a previously published expert classification. Main Outcomes and Measures: The primary outcome for this analysis was the composite of serious and nonserious treatment-related and treatment-unrelated gastrointestinal adverse events. The secondary outcomes were other adverse events and the composite of death or hospital admission due to COVID-19 infection. Logistic regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, heart failure, and myocardial infarction were assessed for effect modification of the association between the randomization arm and the outcomes of interest by drug-drug interaction status. Results: The cohort included 2205 participants in the colchicine arm and 2227 in the placebo arm (median age, 54 [IQR, 47-61] years; 2389 [54%] women). The most common colchicine drug-drug interactions were rosuvastatin (12%) and atorvastatin (10%). In fully adjusted models, the odds of any gastrointestinal adverse event were 1.80 (95% CI, 1.51-2.15) times higher in the colchicine arm than the placebo arm among people without a drug-drug interaction and 1.68 (95% CI, 1.24-2.26) times higher in the colchicine arm than the placebo arm among people with a drug-drug interaction (P = .69 for interaction). Drug-drug interaction status did not significantly modify the effect of colchicine on the composite of COVID-19 hospitalization or death (odds ratio, 0.91; 95% CI, 0.59-1.40 for drug-drug interaction and 0.84; 95% CI, 0.60-1.19 for no drug-drug interaction; P = .80 for interaction). Conclusions and Relevance: In this secondary analysis of the COLCORONA trial, operational classification of drug interactions system class 3 or 4 drug-drug interactions did not appear to significantly increase the risk of colchicine-related adverse effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04322682.

Asunto(s)

COVID-19 , Colchicina , Interacciones Farmacológicas , SARS-CoV-2 , Humanos , Colchicina/efectos adversos , Colchicina/uso terapéutico , Colchicina/farmacocinética , Femenino , Masculino , Persona de Mediana Edad , Método Doble Ciego , Anciano , Tratamiento Farmacológico de COVID-19 , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Pandemias

Asunto(s)

Influenza Pandémica, 1918-1919 , Gripe Humana , Neumonía Viral , Humanos , Masculino , Adulto Joven , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Diagnóstico Diferencial , Disnea/diagnóstico , Disnea/etiología , Pulmón/diagnóstico por imagen , Pulmón/patología , Radiografía Torácica , Fiebre/diagnóstico , Fiebre/etiología , Tos/diagnóstico , Tos/etiología , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Influenza Pandémica, 1918-1919/historia , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Historia del Siglo XX , Historia del Siglo XXI , Monitoreo Epidemiológico , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Preparación para una Pandemia , Vacunas contra la Influenza/administración & dosificación

RESUMEN

This study investigated the roles of P-selectin and Clara cell secretory protein 16 (CC16) levels in the pathogenesis of severe adenovirus (ADV) pneumonia in children and evaluated their ability to predict disease. Fifty-one children (age, 1-5 years) with ADV pneumonia who were admitted to Xiamen Children's Hospital were included in this study and divided into the mild group (24 patients) and severe group (27 patients). A control group comprising healthy children of the same age who underwent routine physical examinations during the same period (30 patients) was also included. The univariate analysis demonstrated that the levels of the white blood cell count and C-reactive protein, procalcitonin, d-dimer, and P-selectin were increased in a severe group compared with a mild group, while CC16 levels were significantly decreased (p < 0.05). The logistic regression analysis revealed that P-selectin and CC16 levels were independent risk factors for severe ADV pneumonia in children. The areas under the ROC curves suggested that P-selectin and CC16 exhibited high predictive value for severe ADV pneumonia. P-selectin values more than 898.58 pg/mL and CC16 values less than 11.355 ng/mL predicted severe ADV pneumonia. P-selectin and CC16 levels are correlated with the severity of ADV pneumonia in children.

Asunto(s)

Selectina-P , Uteroglobina , Humanos , Selectina-P/sangre , Masculino , Femenino , Preescolar , Lactante , Uteroglobina/sangre , Uteroglobina/genética , Biomarcadores/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Neumonía Viral/sangre , Curva ROC , Índice de Severidad de la Enfermedad , Infecciones por Adenovirus Humanos/virología , Infecciones por Adenovirus Humanos/sangre

RESUMEN

PURPOSE: Patients with bacterial, fungal, and viral community-acquired pneumonia (CAP) were studied to determine their metabolic profiles. METHODS: Loop-mediated isothermal amplification technology and nucleic acid sequence-dependent amplification combined with microfluidic chip technology were applied to screen multiple pathogens from respiratory tract samples. Eighteen patients with single bacterial infection (B-CAP), fifteen with single virus infection (V-CAP), twenty with single fungal infection (F-CAP), and twenty controls were enrolled. UHPLC-MS/MS analysis of untargeted serum samples for metabolic profiles. Multiple linear regression and Spearman's rank correlation analysis were used to determine associations between metabolites and clinical parameters. The sensitivity and specificity of the screened metabolites were also examined, along with their area under the curve. RESULTS: The metabolic signatures of patients with CAP infected by bacteria, viruses, and fungi were markedly different from those of controls. The abundances of 45, 56, and 79 metabolites were significantly unbalanced. Among these differential metabolites, 11, 13, and 29 were unique to the B-CAP, V-CAP, and F-CAP groups, respectively. Bacterial infections were the only known causes of disturbances in the pentose and glucuronate and aldarate and ascorbate metabolism interconversions metabolic pathway. CONCLUSIONS: Serum metabolomic techniques based on UHPLC-MS/MS may identify differences between individuals with CAP who have been infected by various pathogens, and they can also build a metabolite signature for early detection of the origin of infection and prompt care.

Asunto(s)

Infecciones Comunitarias Adquiridas , Metabolómica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/diagnóstico , Metabolómica/métodos , Anciano , Neumonía Bacteriana/sangre , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/diagnóstico , Espectrometría de Masas en Tándem/métodos , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/microbiología , Neumonía Viral/virología , Adulto , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión/métodos , Metaboloma , Sensibilidad y Especificidad

RESUMEN

INTRODUCTION: There is still a lack of clinical evidence comprehensively evaluating the effectiveness of antiviral treatments for COVID-19 hospitalized patients. METHODS: A retrospective cohort study was conducted at Beijing You'An Hospital, focusing on patients treated with nirmatrelvir/ritonavir or azvudine. The study employed a tripartite analysis-viral dynamics, survival curve analysis, and AI-based radiological analysis of pulmonary CT images-aiming to assess the severity of pneumonia. RESULTS: Of 370 patients treated with either nirmatrelvir/ritonavir or azvudine as monotherapy, those in the nirmatrelvir/ritonavir group experienced faster viral clearance than those treated with azvudine (5.4 days vs. 8.4 days, p < 0.001). No significant differences were observed in the survival curves between the two drug groups. AI-based radiological analysis revealed that patients in the nirmatrelvir group had more severe pneumonia conditions (infection ratio is 11.1 vs. 5.35, p = 0.007). Patients with an infection ratio higher than 9.2 had nearly three times the mortality rate compared to those with an infection ratio lower than 9.2. CONCLUSIONS: Our study suggests that in real-world studies regarding hospitalized patients with COVID-19 pneumonia, the antiviral effect of nirmatrelvir/ritonavir is significantly superior to azvudine, but the choice of antiviral agents is not necessarily linked to clinical outcomes; the severity of pneumonia at admission is the most important factor to determine prognosis. Additionally, our findings indicate that pulmonary AI imaging analysis can be a powerful tool for predicting patient prognosis and guiding clinical decision-making.

Asunto(s)

Antivirales , Inteligencia Artificial , Tratamiento Farmacológico de COVID-19 , COVID-19 , Ritonavir , SARS-CoV-2 , Humanos , Antivirales/uso terapéutico , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Ritonavir/uso terapéutico , COVID-19/diagnóstico por imagen , COVID-19/mortalidad , SARS-CoV-2/efectos de los fármacos , Anciano , Resultado del Tratamiento , Tomografía Computarizada por Rayos X , Hospitalización , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/mortalidad , Adulto , Pandemias , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/mortalidad , Betacoronavirus/efectos de los fármacos , Combinación de Medicamentos , Pulmón/diagnóstico por imagen , Pulmón/efectos de los fármacos , Pulmón/virología

RESUMEN

INTRODUCTION: Since the emergence of COVID-19, the Malaysian government has made wearing a face mask in public mandatory since August 1, 2020, as an effort by the government to control the transmission of COVID-19. However, Malaysians' willingness to wear face masks in public is unknown. OBJECTIVE: Thus, this study aimed to evaluate their perception of face mask wearing during COVID-19 and its contributing factors. METHODOLOGY: A total of 1024 respondents, aged ≥ 18 years, participated in this online cross-sectional survey from October 2021 to December 2021. The Face Mask Perception Scale (FMPS) was used to measure their perceptions. RESULTS: Most of the respondents perceived wearing a face mask as uncomfortable. Our findings also revealed statistically significant differences and a small effect (f2 = 0.04) in which respondents who were concerned about being infected by the virus perceived face mask wearing appearance positively (B = - 0.09 units of log-transformed, 95% CI = - 0.15, - 0.04), whereas married respondents perceived it negatively (B = 0.07 units of log-transformed, 95% CI = 0.03, 0.09). There were no statistically significant differences in other domains of FMPS. CONCLUSION: In conclusion, discomfort was a major complaint. Marital status and fear of COVID-19 infection affected their perceptions. The public health implications of these findings highlight the importance of addressing discomfort and societal perceptions, particularly those influenced by factors such as marital status and COVID-19 experience, to promote widespread acceptance and consistent usage of face masks, which is crucial in mitigating the spread of COVID-19.

Asunto(s)

COVID-19 , Máscaras , Pandemias , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/psicología , Malasia/epidemiología , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Pandemias/prevención & control , Adulto Joven , Encuestas y Cuestionarios , Adolescente , Neumonía Viral/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/psicología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/psicología , Infecciones por Coronavirus/epidemiología , Percepción , Anciano , Betacoronavirus

RESUMEN

BACKGROUND: The conduct of virtual physical examination has provided significant information for the diagnosis during a teleconsultation session, especially during the COVID-19 pandemic, where in-person physical examinations have been greatly compromised. OBJECTIVE: The aim of this scoping review was to provide a comprehensive overview of the available evidence concerning virtual physical examination (VPE) in all healthcare settings during the COVID-19 pandemic. The review focuses on types of VPE, technological and non-technological approaches, patient and clinician experiences, as well as barriers and facilitators of VPE. METHODS: A literature search was conducted across three databases, namely MEDLINE, Embase, and Scopus. Only studies in the English language with primary research data collected from December 2019 to January 2023 were included. A narrative analysis, highlighting patients' and clinicians' experiences, was conducted on the included studies. This scoping review was reported using The PRISMA extension for scoping reviews (PRISMA-ScR) Checklist. RESULTS: A total of 25 articles meeting eligibility criteria were identified. Three major types of VPE included were musculoskeletal, head and neck, and chest exams. Sixteen studies involved specific technological aids, while three studies involved non-technological aids. Patients found VPE helped them to better assess their disease conditions, or aided their clinicians' understanding of their conditions. Clinicians also reported that VPE had provided enough clinically relevant information for decision-making in 2 neurological evaluations. Barriers to conducting VPE included technological challenges, efficacy concerns, confidence level of assistants, as well as patient health conditions, health literacy, safety, and privacy. CONCLUSIONS: Patients found virtual physical examination (VPE) helpful in understanding their own conditions, and clinicians found it useful for better assessing patient's conditions. From the clinicians' point of view, VPE provided sufficient clinically relevant information for decision-making in neurological evaluations. Major barriers identified for VPE included technological issues, patient's health conditions, and their health literacy.

Asunto(s)

COVID-19 , Pandemias , Examen Físico , Consulta Remota , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Betacoronavirus , Neumonía Viral/epidemiología , Neumonía Viral/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/diagnóstico

RESUMEN

BACKGROUND: During coronavirus disease of 2019 pandemic a standard usage of personal protective equipment (PPE) in healthcare was mandatory, while actually the usage of PPE is currently decreasing. This raises the question about the further use of PPE in the clinical setting because healthcare workers (HCW) are at greater risk of being infected with SARS-CoV-2 than the general population. The primary objective of this study is to determine the proportion of shock room team members approving the further use of PPE including a FFP2 respirator in simulation training and reality. The secondary objectives are to describe the expertise and difficulties faced while using PPE in the shock room care. METHODS: Fifty-four HCW participated in a shock room simulation training at a large urban tertiary care hospital in Germany, utilizing a PPE comprising an FFP2 mask, gloves, goggles, and gown. Subsequently, participants completed an online questionnaire featuring 15 questions presented on a 5-point Likert scale or as multiple-choice questions with predefined answers. RESULTS: Sixty-eight point five percent of our participants voted for an established standard PPE in shock room care. The largest fraction of our participants (40.7%) favors a standard PPE consisting of FFP2 mask, gown, and gloves. Less HCW (31.5%) want to wear PPE in shock room simulation training. Except for goggles we could not detect relevant difficulties faced while using PPE in the shock room environment. Incorrect use of PPE was observed in 14.8%. CONCLUSION: A majority of our participants favored a standard PPE including a FFP2 respirator in shock room care. In addition, we recommend the use of PPE in shock room simulation training, while further awareness of and training in proper use of PPE seems to be necessary to reduce risk of infectious diseases for HCW.

Asunto(s)

COVID-19 , Pandemias , Equipo de Protección Personal , SARS-CoV-2 , Centros de Atención Terciaria , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Pandemias/prevención & control , Masculino , Femenino , Adulto , Personal de Salud/educación , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/epidemiología , Alemania , Neumonía Viral/prevención & control , Neumonía Viral/epidemiología , Encuestas y Cuestionarios , Actitud del Personal de Salud , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Betacoronavirus , Persona de Mediana Edad , Control de Infecciones/métodos

RESUMEN

During the COVID-19 pandemic, wastewater-based epidemiology has proved to be an important tool for monitoring the spread of a disease in a population. Indeed, wastewater surveillance was successfully used as a complementary approach to support public health monitoring schemes and decision-making policies. An essential feature for the estimation of a disease transmission using wastewater data is the distribution of viral shedding rate of individuals in their personal human wastes as a function of the days of their infection. Several candidate shapes for this function have been proposed in literature for SARS-CoV-2. The purpose of the present work is to explore the proposed function shapes and examine their significance on analyzing wastewater SARS-CoV-2 shedding rate data. For this purpose, a simple model is employed applying to medical surveillance and wastewater data of the city of Thessaloniki during a period of Omicron variant domination in 2022. The distribution shapes are normalized with respect to the total virus shedding and then their basic features are investigated. Detailed analysis reveals that the main parameter determining the results of the model is the difference between the day of maximum shedding rate and the day of infection reporting. Since the latter is not part of the distribution shape, the major feature of the distribution affecting the estimation of the number of infected people is the day of maximum shedding rate with respect to the initial infection day. On the contrary, the duration of shedding (total number of disease days) as well as the exact shape of the distribution are by far less important. The incorporation of such wastewater surveillance models in conventional epidemiological models - based on recorded disease transmission data- may improve predictions for disease spread during outbreaks.

Asunto(s)

COVID-19 , SARS-CoV-2 , Esparcimiento de Virus , Aguas Residuales , COVID-19/epidemiología , COVID-19/transmisión , Humanos , Aguas Residuales/virología , Grecia/epidemiología , Pandemias , Monitoreo Epidemiológico Basado en Aguas Residuales , Ciudades , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Betacoronavirus

RESUMEN

Coronaviruses constitute a global threat to human and animal health. It is essential to investigate the long-distance RNA-RNA interactions that approximate remote regulatory elements in strategies, including genome circularization, discontinuous transcription, and transcriptional enhancers, aimed at the rapid replication of their large genomes, pathogenicity, and immune evasion. Based on the primary sequences and modeled RNA-RNA interactions of two experimentally defined coronaviral enhancers, we detected via an in silico primary and secondary structural analysis potential enhancers in various coronaviruses, from the phylogenetically ancient avian infectious bronchitis virus (IBV) to the recently emerged SARS-CoV-2. These potential enhancers possess a core duplex-forming region that could transition between closed and open states, as molecular switches directed by viral or host factors. The duplex open state would pair with remote sequences in the viral genome and modulate the expression of downstream crucial genes involved in viral replication and host immune evasion. Consistently, variations in the predicted IBV enhancer region or its distant targets coincide with cases of viral attenuation, possibly driven by decreased open reading frame (ORF)3a immune evasion protein expression. If validated experimentally, the annotated enhancer sequences could inform structural prediction tools and antiviral interventions.

Asunto(s)

Elementos de Facilitación Genéticos , Genoma Viral , Virus de la Bronquitis Infecciosa , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Virus de la Bronquitis Infecciosa/genética , Humanos , Elementos de Facilitación Genéticos/genética , Animales , ARN Viral/genética , ARN Viral/metabolismo , COVID-19/virología , COVID-19/genética , Betacoronavirus/genética , Replicación Viral/genética , Infecciones por Coronavirus/virología , Transcripción Genética , Regulación Viral de la Expresión Génica , Neumonía Viral/virología

RESUMEN

Severe pneumonia accounts for 15% of the total severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, and the affected patients require hospitalization and oxygen support. In addition, 5% of patients with severe coronavirus disease 2019 (COVID-19) experience acute respiratory distress syndrome and sepsis, which contributes to the high mortality rate. Moreover, the risk of severe COVID-19 increases with age and is the highest among elderly people over 70 years of age. Notably, these pneumonia cases can be attributed to the reactivation of latent cytomegalovirus (CMV). We hereby report two cases of patients with COVID-19 who required prolonged mechanical ventilation and were later diagnosed with secondary CMV pneumonia. These cases support the theory that in some patients with severe COVID-19, there is a possibility of CMV reactivation, contributing to the disease's severity and pathogenesis. These cases also highlight the risk involved in using steroids for a long time and the requirement of routine evaluation for CMV infection in patients with COVID-19 who require prolonged mechanical ventilation or have difficulty weaning off from the ventilator support.

Asunto(s)

COVID-19 , Infecciones por Citomegalovirus , Respiración Artificial , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/diagnóstico , Masculino , Anciano , Persona de Mediana Edad , Femenino , SARS-CoV-2 , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Índice de Severidad de la Enfermedad

Asunto(s)

COVID-19 , Dióxido de Carbono , Terapia de Reemplazo Renal Continuo , Pandemias , SARS-CoV-2 , Uremia , Humanos , COVID-19/complicaciones , COVID-19/terapia , Masculino , Anciano , Terapia de Reemplazo Renal Continuo/métodos , Uremia/terapia , Neumonía Viral/terapia , Neumonía Viral/complicaciones , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/complicaciones , Betacoronavirus

RESUMEN

Background: COVID-19 is a highly challenging infectious disease. Research ethics committees (RECs) have challenges reviewing research on this new pandemic disease under a tight timeline and public pressure. This study aimed to assess RECs' responses and review during the outbreak in seven Asian countries where the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) networks are active. Methods: The online survey was conducted in seven Asian countries from April to August 2021. Two sets of online questionnaires were developed, one set for the chairs/secretaries and another set for the REC members.The REC profiles obtained from the REC members are descriptive in nature. Data from the chairs/secretaries were compared between the RECs with external quality assessment (SIDCER-Recognized RECs, SR-RECs) and non-external quality assessment (Non-SIDCER-Recognized RECs, NSR-RECs) and analyzed using a Chi-squared test. Results: A total of 688 REC members and 197 REC chairs/secretaries participated in the survey. Most RECs have standard operating procedures (SOPs), and have experience in reviewing all types of protocols, but 18.1% had no experience reviewing COVID-19 protocols. Most REC members need specific training on reviewing COVID-19 protocols (93%). In response to the outbreak, RECs used online reviews, increased meeting frequency and single/central REC. All SR-RECs had a member composition as required by the World Health Organisation ethics guidelines, while some NSR-RECs lacked non-affiliated and/or layperson members. SR-RECs reviewed more COVID-related product development protocols and indicated challenges in reviewing risk/benefit and vulnerability (0.010), informed consent form (0.002), and privacy and confidentiality (P = 0.020) than NSR-RECs. Conclusions: Surveyed RECs had a general knowledge of REC operation and played a significant role in reviewing COVID-19-related product development protocols. Having active networks of RECs across regions to share updated information and resources could be one of the strategies to promote readiness for future public health emergencies.

Asunto(s)

COVID-19 , Comités de Ética en Investigación , Pandemias , SARS-CoV-2 , COVID-19/epidemiología , Humanos , Encuestas y Cuestionarios , Asia/epidemiología , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología

RESUMEN

Natural killer (NK) cells play a critical role in virus control. However, it has remained largely unclear whether NK cell mobilization in SARS-CoV-2 infections is beneficial or pathologic. To address this deficit, we employed a validated experimental NK cell depletion non-human primate (NHP) model with SARS-CoV-2 Delta variant B.1.617.2 challenge. Viral loads (VL), NK cell numbers, activation, proliferation, and functional measures were evaluated in blood and tissues. In non-depleted (control) animals, infection rapidly induced NK cell expansion, activation, and increased tissue trafficking associated with VL. Strikingly, we report that experimental NK cell depletion leads to higher VL, longer duration of viral shedding, significantly increased levels of pro-inflammatory cytokines in the lungs, and overt lung damage. Overall, we find the first significant and conclusive evidence for NK cell-mediated control of SARS-CoV-2 virus replication and disease pathology. These data indicate that adjunct therapies for infection could largely benefit from NK cell-targeted approaches.

Asunto(s)

COVID-19 , Células Asesinas Naturales , Pulmón , SARS-CoV-2 , Carga Viral , Replicación Viral , Células Asesinas Naturales/inmunología , Animales , SARS-CoV-2/inmunología , SARS-CoV-2/fisiología , COVID-19/inmunología , COVID-19/virología , Replicación Viral/fisiología , Pulmón/inmunología , Pulmón/virología , Modelos Animales de Enfermedad , Neumonía Viral/inmunología , Neumonía Viral/virología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Macaca mulatta , Betacoronavirus/fisiología , Betacoronavirus/inmunología , Pandemias , Humanos

RESUMEN

Importance: Chronic absenteeism among kindergarten through grade 12 students has increased considerably after the COVID-19 pandemic. Objective: To examine the association between virtual learning during the 2020-2021 school year and chronic absenteeism during the 2021-2022 school year at the school district level. Design, Setting, and Participants: This cross-sectional study used a panel of 11 017 school districts throughout the US comprising kindergarten through grade 12 for the 2018-2019 and 2021-2022 school years. Exposures: The key covariates were the percentage of hybrid and virtual school days in the previous school year, with an assumption that these values in the 2018-2019 school year were zero. Main Outcome and Measures: Chronic absenteeism rates at the district level, which were regressed on the percentage of school days in a learning mode in the previous school year, demographic characteristic and socioeconomic status controls, plus district and year fixed effects. Observations were weighted by district enrollment, and SEs were clustered at the district level. Results: The dataset includes 11 017 school districts for 2 years and 22 034 observations. Chronic absenteeism rates increased by 13.5 percentage points, from a mean (SD) of 15.9% (8.1%) in the 2018-2019 school year to 29.4% (13.2%) in the 2021-2022 school year. Students whose schools had 100% virtual instruction during the COVID-19 pandemic had chronic absenteeism rates that were 6.9 percentage points (95% CI, 4.8-8.9 percentage points) higher than those that were 100% in person. Hybrid instruction was not associated with increased absenteeism. The association between virtual learning and chronic absenteeism varied by socioeconomic status, with the conditional correlation much larger for at-risk students; chronic absenteeism rates were 10.6 percentage points (95% CI, 7.2-14.1 percentage points) higher among students with 100% of days in virtual learning from districts in the top quintile of poverty rates compared with 100% in-persion districts. Conclusions and Relevance: In this cross-sectional study, chronic absenteeism rates were substantially higher in school districts that used virtual learning during the COVID-19 pandemic compared with in person. Understanding how to reduce chronic absenteeism and use virtual learning without potentially negative consequences are key policy questions moving forward.

Asunto(s)

Absentismo , COVID-19 , Educación a Distancia , Pandemias , SARS-CoV-2 , Instituciones Académicas , Humanos , COVID-19/epidemiología , Estudios Transversales , Niño , Masculino , Femenino , Educación a Distancia/métodos , Preescolar , Adolescente , Estados Unidos/epidemiología , Estudiantes/estadística & datos numéricos , Betacoronavirus , Neumonía Viral/epidemiología , Infecciones por Coronavirus/epidemiología

RESUMEN

AIM: Digital inclusion has a positive impact on health and wellbeing through fostering connectivity and access to information. In Aotearoa New Zealand, 4% of older adults live in aged residential care (ARC) facilities and are vulnerable to social isolation. This study explored whether ARC facilities provide opportunities to socially connect online and whether the COVID-19 pandemic affected the provision of these opportunities. METHOD: Information on technology and internet provision from 558 ARC facilities was extracted from facilities' own or related websites in 2019 and 2021. ARC facilities were categorised according to whether they provided digital devices, internet access and internet-based leisure activities, or made no reference to technology. RESULTS: In 2019, 392 (70%) of 558 ARC facilities publicised availability of internet-based technologies for residents; however, only 46 (8%) mentioned providing access to computer devices. In 2021 (during the pandemic), there was a small increase to 421 (76%) and 54 (10%) of facilities respectively. Facilities mentioning internet-based leisure activities were 63 (11%) in 2019 and 55 (10%) in 2021. Those not referring to technology had reduced from 166 (30%) in 2019 to 137 (24%) in 2021. CONCLUSION: Few ARC facilities enabled residents to fully access the digital world, even after periods of isolation due to COVID-19. Aged care providers could be more proactive by providing internet access and digital learning opportunities.

Asunto(s)

COVID-19 , Hogares para Ancianos , Internet , Pandemias , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Nueva Zelanda , Anciano , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Aislamiento Social , Betacoronavirus , Actividades Recreativas

RESUMEN

INTRODUCTION: This descriptive study reviews clinical outcomes of individuals admitted to a northern Canadian, rural intensive care unit (ICU) with severe COVID-19. It reports our site-specific data that is part of an ongoing global effort to gather data and guide therapy; the aims of this study were to describe participants admitted to our ICU with COVID-19 and illuminate challenges faced by rural and remote centres. METHODS: This retrospective study examined data from participants admitted to the ICU with COVID-19 pneumonia between 24th November 2020 and 28th February 2022. Using data from electronic and hardcopy health records, data were obtained according to standardised forms developed for the Short Period Incidence Study of Severe Acute Respiratory Infection. RESULTS: Eighty-five adult participants were admitted to our ICU with COVID-19. The median age of participants was 57 years old (range: 23-83 years); 49.4% were males and 50.6% were females. Of our cohort, 58.9% required mechanical ventilation at some point during their stay and the median duration of stay in our ICU was 5 days (range: 1-36 days). Amongst individuals included, 25.9% were discharged alive from our hospital on their index admission, 57.6% were transferred to another facility and 16.5% died in our facility. CONCLUSION: COVID-19 significantly strained our local ICU resources, necessitating high numbers of patient transfers. However, despite limited resources, patients at our site received contemporary guideline-based care for COVID-19 pneumonia. Future pandemic and surge capacity planning must ensure that rural and remote communities receive adequate additional resources to meet the anticipated needs of their local populations. INTRODUCTION: Cette étude descriptive examine les résultats cliniques des personnes admises dans une unité de soins intensifs rurale du nord du Canada avec une COVID-19 sévère. Elle rapporte des données spécifiques à notre site qui font partie d'un effort global en cours pour rassembler des données et guider la thérapie. Les objectifs de cette étude étaient de décrire les participants admis dans notre unité de soins intensifs avec la COVID-19 et d'éclairer les défis auxquels sont confrontés les centres ruraux et éloignés. MTHODES: Cette étude rétrospective a examiné les données des participants admis à l'unité de soins intensifs pour une pneumonie due à la COIVD-19 entre le 24 novembre 2020 et le 28 février 2022. Les données ont été obtenues à partir de dossiers médicaux électroniques et papier, selon des formulaires standardisés développés pour l'étude d'incidence à court terme des infections respiratoires aiguës sévères (SPRINT-SARI). RSULTATS: 85 participants adultes ont été admis dans notre unité de soins intensifs avec la COVID-19. L'âge médian des participants était de 57 ans (intervalle: 23-83 ans); 49,4% étaient des hommes et 50,6% des femmes. Dans notre cohorte, 58,9% ont eu besoin d'une ventilation mécanique à un moment ou à un autre de leur séjour et la durée médiane du séjour dans notre unité de soins intensifs était de 5 jours (intervalle: 1-36 jours). Parmi les personnes incluses, 25,9% sont sorties vivantes de notre hôpital lors de leur admission initiale, 57,6% ont été transférées dans un autre établissement et 16,5% sont décédées dans notre établissement. CONCLUSION: La COVID-19 a mis à rude épreuve les ressources de notre unité locale de soins intensifs, nécessitant un grand nombre de transferts de patients. Cependant, malgré des ressources limitées, les patients de notre site ont reçu des soins fondés sur des lignes directrices contemporaines pour la pneumonie due à la COVID-19. À l'avenir, la planification de la pandémie et de la capacité de pointe doit garantir que les communautés rurales et éloignées reçoivent des ressources supplémentaires adéquates pour répondre aux besoins anticipés de leurs populations locales.

Asunto(s)

COVID-19 , Unidades de Cuidados Intensivos , Pandemias , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/terapia , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Colombia Británica/epidemiología , Anciano , Anciano de 80 o más Años , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Servicios de Salud Rural/estadística & datos numéricos , Adulto Joven , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Betacoronavirus , Respiración Artificial/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos

RESUMEN

INTRODUCTION: The European Air Transport Command (EATC) is a seven-nation integrated command. One of its core capabilities is strategic aeromedical evacuation (AE). During the global COVID-19 pandemic and Ukrainian crisis, EATC proved that acting in concert is a valuable, effective, and reliable option.METHODS: By pooling and sharing aircraft and personnel, EATC has privileged access to a diverse fleet and pool of experts. Cooperation is based on a common set of rules and regulations, which ensures that EATC can address any problem with expertise.RESULTS: During the COVID-19 pandemic, 1060 COVID-19-positive patients were transported in 198 missions, with neither death nor disease transmission reported during those strategic AE flights. EATC transferred 986 military cases, mostly routine priority (91.4%); the other 74 cases were civilians, who were transported in 17 missions, with 81.1% categorized as urgent. During the Ukrainian crisis, 251 patients were transported, 112 military and 139 civilians, including 30 children. Among the recorded injuries were cerebrocranial, abdominal, and chest injuries, as well as fractures (180) and amputations (48) of the extremities.DISCUSSION: EATC is recognized as a center of expertise within the AE community, where interoperability and harmonization of concepts are key to safety and success. Cross-national missions, where a patient is evacuated by an aircraft and medical crew provided by another nation, offer maximum flexibility. Complex situations, such as the COVID-19 pandemic and the Ukrainian crisis, have shown that multinational cooperation is not only achievable but also provides robust, effective, and reliable solutions for AE in particular.Fiorini A, Vermeltfoort R, Dulaurent E, Hove MG, Borsch M. Cross-national strategic aeromedical evacuation at the European Air Transport Command. Aerosp Med Hum Perform. 2024; 95(9):709-715.

Asunto(s)

Medicina Aeroespacial , Ambulancias Aéreas , COVID-19 , Personal Militar , Pandemias , Humanos , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/prevención & control , Ambulancias Aéreas/organización & administración , Europa (Continente)/epidemiología , SARS-CoV-2 , Ucrania/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/prevención & control , Transporte de Pacientes/organización & administración , Aeronaves