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1.
Front Endocrinol (Lausanne) ; 15: 1342204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948513

RESUMO

Purpose: Chest computed tomography (CT) is used to determine the severity of COVID-19 pneumonia, and pneumonia is associated with hyponatremia. This study aims to explore the predictive value of the semi-quantitative CT visual score for hyponatremia in patients with COVID-19 to provide a reference for clinical practice. Methods: In this cross-sectional study, 343 patients with RT-PCR confirmed COVID-19, all patients underwent CT, and the severity of lung lesions was scored by radiologists using the semi-quantitative CT visual score. The risk factors of hyponatremia in COVID-19 patients were analyzed and combined with laboratory tests. The thyroid function changes caused by SARS-CoV-2 infection and their interaction with hyponatremia were also analyzed. Results: In patients with SARS-CoV-2 infection, the total severity score (TSS) of hyponatremia was higher [M(range), 3.5(2.5-5.5) vs 3.0(2.0-4.5) scores, P=0.001], implying that patients with hyponatremia had more severe lung lesions. The risk factors of hyponatremia in the multivariate regression model included age, vomiting, neutrophils, platelet, and total severity score. SARS-CoV-2 infection impacted thyroid function, and patients with hyponatremia showed a lower free triiodothyronine (3.1 ± 0.9 vs 3.7 ± 0.9, P=0.001) and thyroid stimulating hormone level [1.4(0.8-2.4) vs 2.2(1.2-3.4), P=0.038]. Conclusion: Semi-quantitative CT score can be used as a risk factor for hyponatremia in patients with COVID-19. There is a weak positive correlation between serum sodium and free triiodothyronine in patients with SARS-CoV-2 infection.


Assuntos
COVID-19 , Hiponatremia , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Humanos , COVID-19/complicações , COVID-19/diagnóstico por imagem , Hiponatremia/etiologia , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Idoso , Adulto , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Pandemias , Betacoronavirus , Idoso de 80 Anos ou mais
2.
Medicine (Baltimore) ; 103(27): e38819, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968457

RESUMO

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has manifested with respiratory symptoms and a spectrum of extra-pulmonary complications. Emerging evidence suggests potential impacts on the auditory and vestibular systems, but the extent and nature of these effects in recovered individuals remain unclear. This study aimed to investigate the prevalence and severity of vertigo and hearing impairment in individuals who have recovered from COVID-19 and to identify potential risk factors associated with these sensory symptoms. A cohort of 250 recovered COVID-19 patients was assessed. Standardized questionnaires, including the Dizziness Handicap Inventory and the Vertigo Symptom Scale, were used to evaluate vertigo. Hearing assessment was conducted using pure-tone audiometry, speech audiometry, tympanometry, and oto-acoustic emissions testing. Logistic regression analysis was performed to assess the association between COVID-19 severity and the occurrence of sensory symptoms, controlling for confounding variables such as age and comorbidities. Of the participants, 10% reported vertigo, varying severity. Hearing assessments revealed that most participants had normal hearing, with an average speech discrimination score of 94.6. Logistic regression analysis indicated a significant association between severe COVID-19 and an increased likelihood of vertigo (OR 2.11, 95% CI 1.02-4.35, P = .043) and hearing impairment (OR 3.29, 95% CI 1.60-6.78, P = .002). This study suggests a significant association between COVID-19 severity and vertigo and hearing impairment prevalence. The findings underscore the importance of sensory symptom assessment in the post-recovery phase of COVID-19, highlighting the need for comprehensive healthcare approaches to manage long-term sequelae.


Assuntos
COVID-19 , Perda Auditiva , SARS-CoV-2 , Vertigem , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Vertigem/epidemiologia , Vertigem/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Adulto , Pandemias , Idoso , Prevalência , Índice de Gravidade de Doença , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Fatores de Risco , Betacoronavirus
3.
Front Endocrinol (Lausanne) ; 15: 1345008, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045269

RESUMO

Introduction: This study aimed to determine the frequency of thyroid gland involvement in chest CT scans of patients with COVID-19 admitted to university-affiliated hospitals and assess its relationship with the severity of lung involvement and patient survival in 2020. Material and methods: In this retrospective cross-sectional study, 1000 PCR-positive patients with COVID-19 who were referred to University-affiliated Hospital in 2020 and had chest CT performed within 72 hours of admission to the hospital were examined. The data was collected by patient file information and CT findings recorded in the PACS system, including thyroid involvement, the severity of lung involvement, and findings related to the death and recovery of patients. Results: The mean age of the examined patients was 56 years. 525 people (52.5%) were men, and 475 (47.5%) were women. 14% had severe pulmonary involvement, and 9.3% had very severe involvement. Moreover, 15.9 percent of them had deceased. 19.7% had focal thyroid involvement, 14% had diffuse involvement, and 66.3% were healthy subjects. Male gender and older age showed a significant relationship with thyroid gland involvement. The severity of lung involvement, the death rate in patients, and hospitalization in ICU were also significantly related to thyroid gland involvement in patients with COVID. Discussion and conclusion: This study highlights the importance of considering thyroid-gland involvement in the comprehensive management of COVID-19 patients. Routine screening and monitoring of thyroid-function may facilitate earlier detection and appropriate management of thyroid-related complications, potentially improving clinical outcomes. This study suggests that in COVID-19 infection the monitoring of thyroid function is prudent, particularly in cases of more serious disease.


Assuntos
COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Humanos , COVID-19/diagnóstico por imagem , COVID-19/mortalidade , COVID-19/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Estudos Transversais , Idoso , Adulto , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/mortalidade , Pneumonia Viral/epidemiologia , Pandemias , Doenças da Glândula Tireoide/diagnóstico por imagem , Doenças da Glândula Tireoide/epidemiologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/epidemiologia , Betacoronavirus/isolamento & purificação , Taxa de Sobrevida
4.
PLoS One ; 19(7): e0302413, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38976703

RESUMO

During the COVID-19 pandemic, pneumonia was the leading cause of respiratory failure and death. In addition to SARS-COV-2, it can be caused by several other bacterial and viral agents. Even today, variants of SARS-COV-2 are endemic and COVID-19 cases are common in many places. The symptoms of COVID-19 are highly diverse and robust, ranging from invisible to severe respiratory failure. Current detection methods for the disease are time-consuming and expensive with low accuracy and precision. To address such situations, we have designed a framework for COVID-19 and Pneumonia detection using multiple deep learning algorithms further accompanied by a deployment scheme. In this study, we have utilized four prominent deep learning models, which are VGG-19, ResNet-50, Inception V3 and Xception, on two separate datasets of CT scan and X-ray images (COVID/Non-COVID) to identify the best models for the detection of COVID-19. We achieved accuracies ranging from 86% to 99% depending on the model and dataset. To further validate our findings, we have applied the four distinct models on two more supplementary datasets of X-ray images of bacterial pneumonia and viral pneumonia. Additionally, we have implemented a flask app to visualize the outcome of our framework to show the identified COVID and Non-COVID images. The findings of this study will be helpful to develop an AI-driven automated tool for the cost effective and faster detection and better management of COVID-19 patients.


Assuntos
COVID-19 , Aprendizado Profundo , SARS-CoV-2 , Tomografia Computadorizada por Raios X , COVID-19/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X/métodos , SARS-CoV-2/isolamento & purificação , Pneumonia Viral/diagnóstico por imagem , Pandemias , Algoritmos , Pneumonia/diagnóstico por imagem , Pneumonia/diagnóstico , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico , Internet , Betacoronavirus
5.
PLoS Pathog ; 20(7): e1012039, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950065

RESUMO

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. However, the routes of transmission of the virus to, and from, the mink have been unclear. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. Detailed analysis of changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants with the Y453F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early in the outbreak. However, further introductions of the virus, by variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of viral genome data, we estimate, using a conservative approach, that about 17 separate examples of mink to human transmission occurred in Denmark but up to 59 such events (90% credible interval: (39-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using Bayesian methods. Using the latter approach, 136 jumps (90% credible interval: (117-164)) from humans to mink were found, which may underlie the farm-to-farm spread. Thus, transmission of SARS-CoV-2 from humans to mink, mink to mink, from mink to humans and between humans were all observed.


Assuntos
COVID-19 , Vison , Filogenia , SARS-CoV-2 , Vison/virologia , COVID-19/transmissão , COVID-19/virologia , COVID-19/epidemiologia , COVID-19/veterinária , SARS-CoV-2/genética , Animais , Dinamarca/epidemiologia , Humanos , Pandemias , Fazendas , Betacoronavirus/genética , Betacoronavirus/classificação , Genoma Viral , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/transmissão , Glicoproteína da Espícula de Coronavírus/genética
6.
ACS Chem Biol ; 19(7): 1593-1603, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38980755

RESUMO

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted a critical need to discover more effective antivirals. While therapeutics for SARS-CoV-2 exist, its nonstructural protein 13 (Nsp13) remains a clinically untapped target. Nsp13 is a helicase responsible for unwinding double-stranded RNA during viral replication and is essential for propagation. Like other helicases, Nsp13 has two active sites: a nucleotide binding site that hydrolyzes nucleoside triphosphates (NTPs) and a nucleic acid binding channel that unwinds double-stranded RNA or DNA. Targeting viral helicases with small molecules, as well as the identification of ligand binding pockets, have been ongoing challenges, partly due to the flexible nature of these proteins. Here, we use a virtual screen to identify ligands of Nsp13 from a collection of clinically used drugs. We find that a known ion channel inhibitor, IOWH-032, inhibits the dual ATPase and helicase activities of SARS-CoV-2 Nsp13 at low micromolar concentrations. Kinetic and binding assays, along with computational and mutational analyses, indicate that IOWH-032 interacts with the RNA binding interface, leading to displacement of nucleic acid substrate, but not bound ATP. Evaluation of IOWH-032 with microbial helicases from other superfamilies reveals that it is selective for coronavirus Nsp13. Furthermore, it remains active against mutants representative of observed SARS-CoV-2 variants. Overall, this work provides a new inhibitor for Nsp13 and provides a rationale for a recent observation that IOWH-032 lowers SARS-CoV-2 viral loads in human cells, setting the stage for the discovery of other potent viral helicase modulators.


Assuntos
Antivirais , Reposicionamento de Medicamentos , SARS-CoV-2 , Proteínas não Estruturais Virais , SARS-CoV-2/efeitos dos fármacos , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/farmacologia , Antivirais/química , Humanos , RNA Helicases/metabolismo , RNA Helicases/antagonistas & inibidores , COVID-19/virologia , Ácidos Nucleicos/metabolismo , Ácidos Nucleicos/química , Betacoronavirus/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/antagonistas & inibidores , Metiltransferases
7.
J Cardiothorac Surg ; 19(1): 442, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003456

RESUMO

BACKGROUND: The COVID-19 pandemic was primarily considered a respiratory malady in the early phases of the outbreak. However, as more patients suffer from this illness, a myriad of symptoms emerge in organ systems separate from the lungs. Among those patients with cardiac involvement, myocarditis, pericarditis, myocardial infarction, and arrhythmia were among the most common manifestations. Pericarditis with pericardial effusion requiring medical or interventional treatments has been previously reported in the acute setting. Notably, chronic pericarditis with pericardial thickening resulting in constriction requiring sternotomy and pericardiectomy has not been published to date. CASE PRESENTATION: A patient with COVID-19-associated constrictive pericarditis three years after viral infection requiring pericardiectomy was reported. The COVID-19 infection originally manifested as anosmia and ageusia. Subsequently, the patient developed dyspnea, fatigue, right-sided chest pressure, bilateral leg edema, and abdominal fullness. Following recurrent right pleural effusions and a negative autoimmune work-up, the patient was referred for cardiothoracic surgery for pericardiectomy when radiographic imaging and hemodynamic assessment were consistent with constrictive pericarditis. Upon median sternotomy, the patient's pericardium was measured to be 8 mm thick. Descriptions of the clinical, diagnostic, and therapeutic features are provided. Within the first week after the operation, the patient's dyspnea resolved; one month later, leg edema and abdominal bloating were relieved. CONCLUSIONS: Although an association between COVID-19 and cardiac complications has been established, this case adds another element of virus severity and chronic manifestations. The need for sternotomy and pericardiectomy to treat COVID-19-related constrictive pericarditis is believed to be the first reported diagnosis.


Assuntos
COVID-19 , Pericardiectomia , Pericardite Constritiva , SARS-CoV-2 , Humanos , Pericardite Constritiva/cirurgia , Pericardite Constritiva/diagnóstico , COVID-19/complicações , Pericardiectomia/métodos , Masculino , Pandemias , Pneumonia Viral/complicações , Infecções por Coronavirus/complicações , Pessoa de Meia-Idade , Betacoronavirus , Tomografia Computadorizada por Raios X
8.
J Pak Med Assoc ; 74(6 (Supple-6)): S13-S17, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39018133

RESUMO

OBJECTIVE: To evaluate the factors associated with mortality among coronavirus disease-2019 patients with preexisting hypertension. METHODS: The retrospective, cross-sectional study was conducted from June 15 to July 7, 2021, after approval from Dr Soetomo General Province Hospital, Indonesia, and comprised data from the coronavirus disease-2019 registry in the East Java province of Indonesia from March 2020 to June 2021. Data was collected for adult patients infected by coronavirus disease-2019 with pre-existing hypertension Data was analysed using SPSS 23. RESULTS: Of the 2,732 patients in the registry, 425(15.6%) with median age 56.5 years (interquartile range: 50-64 years) had pre-existing hypertension. Of them, 251(59.06%) were males, and 110(25.9%) had died while in hospital. Mortality was associated with older age; higher white blood cell counts at admission and lower platelet count (p<0.05). In addition, electrocardiogram parameters associated with mortality were faster heart rate and ST abnormality (p<0.05). CONCLUSIONS: Older age, high white blood cell level, lower platelet count, faster heart rate, and ST abnormality at admission were found to be the predictors of mortality among hospitalised coronavirus disease-2019 patients with pre-existing hypertension.


Assuntos
COVID-19 , Eletrocardiografia , Hipertensão , Pandemias , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/complicações , COVID-19/epidemiologia , Masculino , Pessoa de Meia-Idade , Indonésia/epidemiologia , Feminino , Hipertensão/epidemiologia , Hipertensão/mortalidade , Hipertensão/complicações , Estudos Transversais , Estudos Retrospectivos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/diagnóstico , Betacoronavirus , Idoso , Fatores Etários , Adulto , Contagem de Leucócitos , Fatores de Risco , Contagem de Plaquetas , Mortalidade Hospitalar
9.
J Zhejiang Univ Sci B ; 25(7): 628-632, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39011682

RESUMO

Airborne transmission is among the most frequent types of nosocomial infection. Recent years have witnessed frequent outbreaks of airborne diseases, such as severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome (MERS) in 2012, and coronavirus disease 2019 (COVID-19), with the latter being on the rampage since the end of 2019 and bringing the effect of aerosols on health back to the fore (Gralton et al., 2011; Wang et al., 2021). An increasing number of studies have shown that certain highly transmissible pathogens can maintain long-term stability and efficiently spread through aerosols (Leung, 2021; Lv et al., 2021). As reported previously, influenza viruses that can spread efficiently through aerosols remain stable for a longer period compared to those that cannot. The World Health Organization (WHO) has stated that aerosol-generating procedures (AGPs) play an important role in aerosol transmission in hospitals (Calderwood et al., 2021). AGPs, referring to medical procedures that produce aerosols, including dental procedures, endotracheal intubation, sputum aspiration, and laparoscopic surgeries, have been reported to be significantly associated with an increased risk of nosocomial infection among medical personnel (Hamilton, 2021).


Assuntos
Aerossóis , COVID-19 , Infecção Hospitalar , Endoscópios , SARS-CoV-2 , Humanos , Infecção Hospitalar/transmissão , Infecção Hospitalar/prevenção & controle , COVID-19/transmissão , SARS-CoV-2/isolamento & purificação , Pandemias , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Desinfecção/métodos , Betacoronavirus , Microbiologia do Ar
10.
Zool Res ; 45(4): 747-766, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38894519

RESUMO

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.


Assuntos
COVID-19 , Modelos Animais de Doenças , Pandemias , SARS-CoV-2 , Animais , COVID-19/imunologia , COVID-19/terapia , SARS-CoV-2/imunologia , Humanos , Camundongos , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pneumonia Viral/terapia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/terapia , Betacoronavirus/imunologia , Cricetinae
11.
Nutrients ; 16(11)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38892564

RESUMO

Patients hospitalized with COVID-19 have low levels of vitamins and trace elements. This could lead to a post-acute COVID-19 condition (PCC) that can worsen a patient's quality of life. We aimed to study the baseline micronutrient status of patients and assess whether a multiple micronutrient supplement (MMS) taken for 2 weeks at the first sign of COVID-19 symptoms would be able to reduce the incidence of PCC. This double-blind, placebo-controlled, randomized clinical trial was conducted in adult outpatients with acute COVID-19, recruited between 2021 and 2023 in Spain. Of the 285 patients assessed for eligibility, 267 were randomized and 246 were included in the intent-to-treat population. The mean age was 46.8 years, and 68% were female. Overall, 54.6% had micronutrient deficiencies in the acute phase of COVID-19 at baseline, and 26.2% had PCC after 180 days of follow-up (D180). The most frequently recorded PCC symptoms were neurological (14.1%), with 24% patients scoring worse in the cognitive tests compared to their baseline status. The rate of PCC at D180 was similar between the placebo (25.0%) and intervention (27.7%) groups, without significant differences (p = 0.785). Age over 50 years was the most relevant risk factor for developing PCC, followed by female sex. The most important protective factor against PCC was SARS-CoV-2 vaccination. In this population of predominantly middle-aged, white women with acute COVID-19 not requiring hospital admission, MMS intake for 14 days at symptom onset did not prevent PCC nor improve their micronutrient status at D180.


Assuntos
COVID-19 , Suplementos Nutricionais , Micronutrientes , SARS-CoV-2 , Humanos , Feminino , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/complicações , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Micronutrientes/administração & dosagem , Adulto , Espanha/epidemiologia , Síndrome de COVID-19 Pós-Aguda , Idoso , Betacoronavirus
12.
Viruses ; 16(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38932199

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense, single-stranded RNA genome-containing virus which has infected millions of people all over the world. The virus has been mutating rapidly enough, resulting in the emergence of new variants and sub-variants which have reportedly been spread from Wuhan city in China, the epicenter of the virus, to the rest of China and all over the world. The occurrence of mutations in the viral genome, especially in the viral spike protein region, has resulted in the evolution of multiple variants and sub-variants which gives the virus the benefit of host immune evasion and thus renders modern-day vaccines and therapeutics ineffective. Therefore, there is a continuous need to study the genetic characteristics and evolutionary dynamics of the SARS-CoV-2 variants. Hence, in this study, a total of 832 complete genomes of SARS-CoV-2 variants from the cities of Taiyuan and Wuhan in China was genetically characterized and their phylogenetic and evolutionary dynamics studied using phylogenetics, genetic similarity, and phylogenetic network analyses. This study shows that the four most prevalent lineages in Taiyuan and Wuhan are as follows: the Omicron lineages EG.5.1.1, followed by HK.3, FY.3, and XBB.1.16 (Pangolin classification), and clades 23F (EG.5.1), followed by 23H (HK.3), 22F (XBB), and 23D (XBB.1.9) (Nextclade classification), and lineage B followed by the Omicron FY.3, lineage A, and Omicron FL.2.3 (Pangolin classification), and the clades 19A, followed by 22F (XBB), 23F (EG.5.1), and 23H (HK.3) (Nextclade classification), respectively. Furthermore, our genetic similarity analysis show that the SARS-CoV-2 clade 19A-B.4 from Wuhan (name starting with 412981) has the least genetic similarity of about 95.5% in the spike region of the genome as compared to the query sequence of Omicron XBB.2.3.2 from Taiyuan (name starting with 18495234), followed by the Omicron FR.1.4 from Taiyuan (name starting with 18495199) with ~97.2% similarity and Omicron DY.3 (name starting with 17485740) with ~97.9% similarity. The rest of the variants showed ≥98% similarity with the query sequence of Omicron XBB.2.3.2 from Taiyuan (name starting with 18495234). In addition, our recombination analysis results show that the SARS-CoV-2 variants have three statistically significant recombinant events which could have possibly resulted in the emergence of Omicron XBB.1.16 (recombination event 3), FY.3 (recombination event 5), and FL.2.4 (recombination event 7), suggesting some very important information regarding viral evolution. Also, our phylogenetic tree and network analyses show that there are a total of 14 clusters and more than 10,000 mutations which may have probably resulted in the emergence of cluster-I, followed by 47 mutations resulting in the emergence of cluster-II and so on. The clustering of the viral variants of both cities reveals significant information regarding the phylodynamics of the virus among them. The results of our temporal phylogenetic analysis suggest that the variants of Taiyuan have likely emerged as independent variants separate from the variants of Wuhan. This study, to the best of our knowledge, is the first ever genetic comparative study between Taiyuan and Wuhan cities in China. This study will help us better understand the virus and cope with the emergence and spread of new variants at a local as well as an international level, and keep the public health authorities informed for them to make better decisions in designing new viral vaccines and therapeutics. It will also help the outbreak investigators to better examine any future outbreak.


Assuntos
COVID-19 , Evolução Molecular , Genoma Viral , Mutação , Filogenia , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/classificação , China/epidemiologia , Humanos , COVID-19/virologia , COVID-19/epidemiologia , Glicoproteína da Espícula de Coronavírus/genética , Cidades , Betacoronavirus/genética , Betacoronavirus/classificação
13.
Bull Exp Biol Med ; 176(6): 767-771, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38890215

RESUMO

The levels of endothelins were assessed in menopausal women with arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) in the acute phase of the moderate COVID-19. Women under observation (age 45-69 years) were divided into two groups. Control group consisted of women (n=16) who did not have COVID-19, were not vaccinated, and had no antibodies to SARS-CoV-2 (IgG). The main group included women (n=63) in the acute phase of the moderate COVID-19 accompanied by pneumonia. According to the clinical and anamnestic data analysis, the main group was divided into subgroups: without AH and T2DM (n=21); with AH and without T2DM (n=32); and with AH and T2DM (n=10). The parameters of clinical blood analysis, as well as endothelin-1, endothelin-2, and endothelin-3 levels were assessed. In women with a moderate COVID-19, the endothelin-1 and endothelin-2 levels were increased compared to the control regardless of AH and T2DM status. We found no statistically significant differences in the studied parameters of endothelial dysfunction between the subgroups of menopausal women in the acute phase of the moderate COVID-19.


Assuntos
COVID-19 , Comorbidade , Diabetes Mellitus Tipo 2 , Endotelinas , Hipertensão , Menopausa , SARS-CoV-2 , Humanos , COVID-19/sangue , COVID-19/complicações , COVID-19/epidemiologia , Feminino , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Pessoa de Meia-Idade , Hipertensão/sangue , Hipertensão/epidemiologia , Idoso , Menopausa/sangue , Endotelinas/sangue , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Pandemias , Endotelina-1/sangue , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia
14.
PLoS Pathog ; 20(6): e1011777, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38913740

RESUMO

COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly understood, largely due to the lack of suitable animal models that recapitulate key clinical and pathological symptoms. Here, we fully characterized AC70 line of human ACE2 transgenic (AC70 hACE2 Tg) mice for SARS-CoV-2 infection. We noted that this model is highly permissive to SARS-CoV-2 with values of 50% lethal dose and infectious dose as ~ 3 and ~ 0.5 TCID50 of SARS-CoV-2, respectively. Mice infected with 105 TCID50 of SARS-CoV-2 rapidly succumbed to infection with 100% mortality within 5 days. Lung and brain were the prime tissues harboring high viral titers, accompanied by histopathology. However, viral RNA and inflammatory mediators could be detectable in other organs, suggesting the nature of a systemic infection. Lethal challenge of AC70 hACE2 Tg mice caused acute onset of leukopenia, lymphopenia, along with an increased neutrophil-to-lymphocyte ratio (NLR). Importantly, infected animals recapitulated key features of COVID-19-associated coagulopathy. SARS-CoV-2 could induce the release of circulating neutrophil extracellular traps (NETs), along with activated platelet/endothelium marker. Immunohistochemical staining with anti-platelet factor-4 (PF4) antibody revealed profound platelet aggregates especially within blocked veins of the lungs. We showed that acute SARS-CoV-2 infection triggered a hypercoagulable state coexisting with ill-regulated fibrinolysis. Finally, we highlighted the potential role of Annexin A2 (ANXA2) in fibrinolytic failure. ANXA2 is a calcium-dependent phospholipid-binding protein that forms a heterotertrameric complexes localized at the extracellular membranes with two S100A10 small molecules acting as a co-receptor for tissue-plasminogen activator (t-PA), tightly involved in cell surface fibrinolysis. Thus, our results revealing elevated IgG type anti-ANXA2 antibody production, downregulated de novo ANXA2/S100A10 synthesis, and reduced ANXA2/S100A10 association in infected mice, this protein might serve as druggable targets for development of antithrombotic and/or anti-fibrinolytic agents to attenuate pathogenesis of COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Modelos Animais de Doenças , Camundongos Transgênicos , SARS-CoV-2 , Animais , COVID-19/patologia , COVID-19/complicações , COVID-19/virologia , COVID-19/metabolismo , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Humanos , Transtornos da Coagulação Sanguínea/virologia , Transtornos da Coagulação Sanguínea/patologia , Pneumonia Viral/virologia , Pneumonia Viral/patologia , Pneumonia Viral/metabolismo , Betacoronavirus , Pulmão/virologia , Pulmão/patologia , Pulmão/metabolismo , Infecções por Coronavirus/virologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/complicações , Pandemias , Armadilhas Extracelulares/metabolismo
15.
J Cardiothorac Surg ; 19(1): 358, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915030

RESUMO

BACKGROUND: Infective endocarditis (IE) is a rare cardiovascular complication in patients with coronavirus disease 2019 (COVID-19). IE after COVID-19 can also be complicated by acute respiratory distress syndrome (ARDS); however, the guidelines for the treatment of such cases are not clear. Here, we report a case of perioperative management of post-COVID-19 IE with ARDS using veno-venous extracorporeal membrane oxygenation (V-V ECMO). CASE PRESENTATION: The patient was a 40-year-old woman who was admitted on day 18 of COVID-19 onset and was administered oxygen therapy, remdesivir, and dexamethasone. The patient's condition improved; however, on day 24 of hospitalization, the patient developed hypoxemia and was admitted to the intensive care unit (ICU) due to respiratory failure. Blood culture revealed Corynebacterium striatum, and transesophageal echocardiography revealed vegetation on the aortic and mitral valves. Valve destruction was mild, and the cause of respiratory failure was thought to be ARDS. Despite continued antimicrobial therapy, ARDS did not improve the patient's condition, and valve destruction progressed; therefore, surgical treatment was scheduled on day 13 of ICU admission. After preoperative consultation with the team, a decision was made to initiate V-V ECMO after the patient was weaned from CPB, with concerns about further worsening of her respiratory status after surgery. The patient returned to the ICU with transition to V-V ECMO, and her circulation remained stable. The patient was weaned off V-V ECMO on postoperative day 33 and discharged from the ICU on postoperative day 47. CONCLUSIONS: ARDS may occur in patients with IE after COVID-19. Owing to concerns about further exacerbation of pulmonary damage, the timing of surgery should be comprehensively considered. Preoperatively, clinicians should discuss perioperative ECMO introduction and configuration.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Assistência Perioperatória , Síndrome do Desconforto Respiratório , Humanos , Feminino , Oxigenação por Membrana Extracorpórea/métodos , Adulto , COVID-19/complicações , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Assistência Perioperatória/métodos , SARS-CoV-2 , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Endocardite/complicações , Endocardite/cirurgia , Ecocardiografia Transesofagiana , Betacoronavirus
16.
J Health Popul Nutr ; 43(1): 96, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926733

RESUMO

Measures such as education, improving knowledge, attitude and taking preventive action to protect against COVID-19 are vital strategies for prevention. The aim of this study was to determine the predictability of Health Belief Model (HBM) constructs in performing preventive behaviors against COVID-19 among secondary school students in Chabahar, Iran. In this cross-sectional-analytical study, 400 secondary school students of Chabahar city were investigated by simple random sampling. The data collection tool was a questionnaire including demographic characteristics, knowledge, behavior, and Health Belief Model constructs' questions. Exploratory Factor Analysis (EFA) was used to evaluate the validity of HBM constructs, and the structural equation modeling (SEM) method was used to evaluate the direct and indirect effects of the relationship between knowledge, HBM constructs, and preventive behavior against COVID-19 based on the conceptual model. Based on the results of the structural modeling, the direct effect of knowledge on the constructs of the health belief model was positive and significant (ß = 0.34, P-value < 0.001), and on the preventive behavior of students was insignificant (ß = 0.12, P-value = 0.07) while the indirect effect of knowledge through increasing the constructs of the HBM on student behavior was positive and significant (ß = 0.30, P < 0.001). The relationship between the constructs of the HBM constructs and student behavior was also positive and significant (ß = 0.89, P-value < 0.001).Due to the fact that knowledge and HBM structures played a role in predicting the adoption of preventive behavior from COVID-19, it is possible to design appropriate interventions to increase knowledge, sensitivity, perceived severity, and self-efficacy, in order to recover from COVID-19 by adopting preventive behaviors.


Assuntos
COVID-19 , Comportamentos Relacionados com a Saúde , Modelo de Crenças de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Análise de Classes Latentes , SARS-CoV-2 , Estudantes , Humanos , COVID-19/prevenção & controle , Feminino , Masculino , Adolescente , Estudos Transversais , Irã (Geográfico) , Estudantes/psicologia , Inquéritos e Questionários , Pandemias/prevenção & controle , Instituições Acadêmicas , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/psicologia , Betacoronavirus , Análise Fatorial
17.
Mol Med ; 30(1): 92, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898389

RESUMO

BACKGROUND: COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. PURPOSE: This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. METHODS: An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. RESULTS: The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. CONCLUSIONS: Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.


Assuntos
COVID-19 , Doenças Cardiovasculares , Pandemias , SARS-CoV-2 , Humanos , COVID-19/complicações , Doenças Cardiovasculares/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pneumonia Viral/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Betacoronavirus , Miocardite/etiologia , Miocardite/virologia
18.
J Investig Med High Impact Case Rep ; 12: 23247096241260959, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38869108

RESUMO

Patients infected with COVID-19 can develop coinfections or acute respiratory disorder that result in ventilation. Dexmedetomidine is a common medication used to sedate ventilated patients in the intensive care unit and for nonintubated patients prior to a surgical procedure. As a highly selective alpha-2 agonist, dexmedetomidine provides sedation while reducing the need for anxiolytics or opioids. However, previous case reports suggest dexmedetomidine can induce fever in a variety of conditions. The purpose of this case report is to describe a patient who acquired a fever of 42.6°C in the setting of COVID-19 after administration of dexmedetomidine.


Assuntos
COVID-19 , Dexmedetomidina , Febre , Hipnóticos e Sedativos , SARS-CoV-2 , Humanos , Dexmedetomidina/efeitos adversos , COVID-19/complicações , Febre/induzido quimicamente , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/complicações , Betacoronavirus , Pessoa de Meia-Idade , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Febre Medicamentosa
19.
Antiviral Res ; 228: 105921, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38825019

RESUMO

The SARS-CoV-2 pandemic has bolstered unprecedented research efforts to better understand the pathogenesis of coronavirus (CoV) infections and develop effective therapeutics. We here focus on non-structural protein nsp15, a hexameric component of the viral replication-transcription complex (RTC). Nsp15 possesses uridine-specific endoribonuclease (EndoU) activity for which some specific cleavage sites were recently identified in viral RNA. By preventing accumulation of viral dsRNA, EndoU helps the virus to evade RNA sensors of the innate immune response. The immune-evading property of nsp15 was firmly established in several CoV animal models and makes it a pertinent target for antiviral therapy. The search for nsp15 inhibitors typically proceeds via compound screenings and is aided by the rapidly evolving insight in the protein structure of nsp15. In this overview, we broadly cover this fascinating protein, starting with its structure, biochemical properties and functions in CoV immune evasion. Next, we summarize the reported studies in which compound screening or a more rational method was used to identify suitable leads for nsp15 inhibitor development. In this way, we hope to raise awareness on the relevance and druggability of this unique CoV protein.


Assuntos
Antivirais , COVID-19 , Endorribonucleases , SARS-CoV-2 , Proteínas não Estruturais Virais , Antivirais/farmacologia , Endorribonucleases/metabolismo , Endorribonucleases/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Humanos , SARS-CoV-2/efeitos dos fármacos , Animais , COVID-19/virologia , Replicação Viral/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Betacoronavirus/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , Pandemias , RNA Viral/genética , Evasão da Resposta Imune
20.
Biochem Biophys Res Commun ; 724: 150231, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38852502

RESUMO

Human coronaviruses are a group of pathogens that primarily cause respiratory and intestinal diseases. Infection can easily cause respiratory symptoms, as well as a variety of serious complications. There are several types of human coronaviruses, such as SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, and SARS-CoV-2. The prevalence of COVID-19 has led to a growing focus on drug research against human coronaviruses. The main protease (Mpro) from human coronaviruses is a relatively conserved that controls viral replication. X77 was discovered to have extremely high inhibitory activity against SARS-CoV-2 Mpro through the use of computer-simulated docking. In this paper, we have resolved the crystal structure of the HCoV-NL63 Mpro complexed with X77 and analyzed their interaction in detail. This data provides essential information for solving their binding modes and their structural determinants. Then, we compared the binding modes of X77 with SARS-CoV-2 Mpro and HCoV-NL63 Mpro in detail. This study illustrates the structural basis of HCoV-NL63 Mpro binding to the inhibitor X77. The structural insights derived from this study will inform the development of new drugs with broad-spectrum resistance to human coronaviruses.


Assuntos
Antivirais , Proteases 3C de Coronavírus , Coronavirus Humano NL63 , SARS-CoV-2 , Humanos , SARS-CoV-2/enzimologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Cristalografia por Raios X , Antivirais/química , Antivirais/farmacologia , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Inibidores de Proteases/metabolismo , Ligação Proteica , Modelos Moleculares , Sítios de Ligação , COVID-19/virologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/antagonistas & inibidores , Betacoronavirus/enzimologia , Conformação Proteica
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