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1.
Viruses ; 13(12)2021 11 28.
Article in English | MEDLINE | ID: mdl-34960652

ABSTRACT

Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.


Subject(s)
Coenzyme A Ligases/antagonists & inhibitors , Coenzyme A Ligases/metabolism , Coronavirus Infections/therapy , Ferroptosis , Animals , Coenzyme A Ligases/genetics , Cytokines/metabolism , Disease Models, Animal , Genes, Viral , Lung Injury/pathology , Macrophages , Mice , Mice, Inbred C57BL , Murine hepatitis virus , Quinoxalines , RAW 264.7 Cells , Spiro Compounds , Toll-Like Receptor 4 , Virus Replication/genetics
2.
Eur Rev Med Pharmacol Sci ; 25(19): 5947-5964, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34661254

ABSTRACT

The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak has resulted in coronavirus disease 2019 (COVID-19) pandemic worldwide, affecting millions of lives. Although vaccines are presently made available, and vaccination drive is in progress to immunize a larger population; still the risk of SARS-CoV-2 infection and related mortality is persistent amid threats of the third wave of the ongoing pandemic. In the scenario of unavailability of robust and efficient treatment modalities, it becomes essential to understand the mechanism of action of the virus and deeply study the molecular mechanisms (both at the virus level and the host level) underlying the infection processes. Recent studies have shown that coronaviruses (CoVs) cause-specific epigenetic changes in the host cells to create a conducive microenvironment for replicating, assembling, and spreading. Epigenetic mechanisms can contribute to various aspects of the SARS-CoV-2 multiplication cycle, like expressing cytokine genes, viral receptor ACE2, and implicating different histone modifications. For SARS-CoV-2 infection, viral proteins are physically associated with various host proteins resulting in numerous interactions between epigenetic enzymes (i.e., histone deacetylases, bromodomain-containing proteins). The involvement of epigenetic mechanisms in the virus life cycle and the host immune responses to control infection result in epigenetic factors recognized as emerging prognostic COVID-19 biomarkers and epigenetic modulators as robust therapeutic targets to curb COVID-19. Therefore, this narrative review aimed to summarize and discuss the various epigenetic mechanisms that control gene expression and how these mechanisms are altered in the host cells during coronavirus infection. We also discuss the opportunities to exploit these epigenetic changes as therapeutic targets for SARS-CoV-2 infection. Epigenetic alterations and regulation play a pivotal role at various levels of coronavirus infection: entry, replication/transcription, and the process of maturation of viral proteins. Coronaviruses modulate the host epigenome to escape the host immune mechanisms. Therefore, host epigenetic alterations induced by CoVs can be considered to develop targeted therapies for COVID-19.


Subject(s)
COVID-19/genetics , COVID-19/therapy , Coronavirus Infections/genetics , Coronavirus Infections/therapy , Epigenesis, Genetic/genetics , Epigenome , Host-Pathogen Interactions , Humans
3.
Viruses ; 13(8)2021 07 31.
Article in English | MEDLINE | ID: mdl-34452378

ABSTRACT

Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children hospitalized with clinical pneumonia and among community controls living in countries with a high HIV burden, namely South Africa and Zambia, between August 2011 to October 2013. Nasopharyngeal/oropharyngeal swabs were collected from all cases and controls and tested for endemic HCoV species and 12 other respiratory viruses using a multiplex real-time PCR assay. We found that the likelihood of detecting endemic HCoV species was higher among asymptomatic controls than cases (11% vs. 7.2%; 95% CI: 1.2-2.0). This was however only observed among children > 6 months and was mainly driven by the Betacoronavirus endemic species (HCoV-OC43 and -HKU1). Endemic HCoV species were detected through the year; however, in Zambia, the endemic Betacoronavirus species tended to peak during the winter months (May-August). There was no association between HIV status and endemic HCoV detection.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Coronavirus/physiology , Case-Control Studies , Child , Child, Preschool , Coronavirus/classification , Coronavirus/genetics , Coronavirus/isolation & purification , Coronavirus Infections/therapy , Hospitalization , Humans , Infant , Male , Nasopharynx/virology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Seasons , South Africa/epidemiology , Zambia/epidemiology
5.
Multimedia | Multimedia Resources | ID: multimedia-9005

ABSTRACT

Em 2021, a Agência Nacional de Vigilância Sanitária aprovou o uso emergencial de dois medicamentos contra a COVID-19 que utilizam combinações de anticorpos monoclonais produzidos em laboratório. Além da COVID-19, os anticorpos monoclonais também têm sido aplicados na terapia de outras doenças, como câncer de mama. Neste vídeo, a equipe COVID-19 DivulgAÇÃO Científica conversa com Adriano Defini Andricopulo, da Universidade de São Paulo, que explica o funcionamento dos medicamentos com anticorpos monoclonais, sua eficácia contra o novo coronavírus e também suas limitações de uso.


Subject(s)
Coronavirus Infections/therapy , Neoplasms/therapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/adverse effects , e-Accessibility
6.
AAPS PharmSciTech ; 22(5): 173, 2021 Jun 08.
Article in English | MEDLINE | ID: mdl-34105037

ABSTRACT

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Middle East Respiratory Syndrome Coronavirus/immunology , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/immunology , Camelus/virology , Chiroptera/virology , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Saudi Arabia/epidemiology , Viral Zoonoses/epidemiology , Viral Zoonoses/immunology , Viral Zoonoses/transmission
8.
Rev. medica electron ; 43(3): 601-615, 2021. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1289807

ABSTRACT

RESUMEN Introducción: una serie temporal es el producto de la observación de una variable en el tiempo. Es una herramienta matemática que se aplica con frecuencia en la salud. No se han elaborado modelos temporales que predigan el comportamiento de los pacientes durante su ingreso en la Unidad de Cuidados Intensivos. Objetivos: crear una serie temporal que permita predecir el comportamiento, durante su ingreso en la Unidad de Cuidados Intensivos, de pacientes graves producto de la covid-19 en la región de Lombardía, Italia. Materiales y métodos: analítico, longitudinal prospectivo con un grupo de pacientes críticos que ingresaron del 1 de abril al 1 de mayo de 2020, con diagnóstico de covid-19, en el Hospital Mayor de Crema, en la región de Lombardía, Italia. El universo estuvo constituido por 28 pacientes y se trabajó con el total de ellos. Resultados: composición por sexo: 48 % masculino. Media de edad: 83 años. Serie temporal: Modelo 1 que ajusta (Hold) PO2/FiO2 p = 0,251; Modelo 2 (ARIMA) SatO2/FiO2 p = 0,674 (en los dos primeros modelos el resultado se incrementó con los días, siguiendo un comportamiento predecible); Modelo 3 (ARIMA) p = 0,406 (en este caso, el resultado esperado decreció a medida que transcurrió el tiempo). Las funciones obtenidas permiten calcular el valor esperado según el día desde el ingreso. Conclusiones: predecir la evolución del paciente en la Unidad de Cuidados Intensivos permitió detectar tempranamente aquellos con una curva inesperada y dirigir hacia a ellos las terapéuticas más agresivas (AU).


ABSTRACT Introduction: a time series is the product of the observation of a variable in time. It is a mathematical tool frequently applied in health. No temporal models have been developed to predict patients' behavior during their staying in the Intensive Care Unit. Objectives: to create a time series allowing to predict the behavior of seriously-ill patients due to COVID-19, during their staying in the Intensive Care Unit in the region of Lombardy, Italy. Materials and methods: analytic, longitudinal prospective study with a group of critical patients who were admitted from April 1st to May 1st, with COVID-19 diagnosis, to Ospedale Maggiore di Crema, in the Lombardy region, Italy. The universe was formed by 28 patients and all of them were worked on. Results: 48% of patients were male. Average age: 83 years; Time series: Model 1 holding PO2/FiO2 p = 0.251; Model 2 (ARIMA) SatO2/FiO2 p = 0.674 (in the two first models the result increased with the days, following a predictable behavior=; Model 3 (ARIMA) p = 0.406 (in this case the expected result decreased as time passed). The obtained functions allow to calculate the expected value according to the day from the admission. Conclusions: predicting patient's evolution in the Intensive Care Unit allowed early detecting those with unexpected curves and targeting more aggressive therapies toward them (AU).


Subject(s)
Humans , Male , Female , Coronavirus Infections/complications , Inpatients/classification , Coronavirus Infections/rehabilitation , Coronavirus Infections/therapy , Coronavirus Infections/epidemiology , Index , Forecasting/methods , Intensive Care Units
9.
Molecules ; 26(9)2021 Apr 29.
Article in English | MEDLINE | ID: mdl-33947034

ABSTRACT

MERS-CoV was identified for the first time in Jeddah, Saudi Arabia in 2012 in a hospitalized patient. This virus subsequently spread to 27 countries with a total of 939 deaths and 2586 confirmed cases and now has become a serious concern globally. Camels are well known for the transmission of the virus to the human population. In this report, we have discussed the prediction, designing, and evaluation of potential siRNA targeting the ORF1ab gene for the inhibition of MERS-CoV replication. The online software, siDirect 2.0 was used to predict and design the siRNAs, their secondary structure and their target accessibility. ORF1ab gene folding was performed by RNAxs and RNAfold software. A total of twenty-one siRNAs were selected from 462 siRNAs according to their scoring and specificity. siRNAs were evaluated in vitro for their cytotoxicity and antiviral efficacy in Huh7 cell line. No significant cytotoxicity was observed for all siRNAs in Huh7 cells. The in vitro study showed the inhibition of viral replication by three siRNAs. The data generated in this study provide preliminary and encouraging information to evaluate the siRNAs separately as well as in combination against MERS-CoV replication in other cell lines. The prediction of siRNAs using online software resulted in the filtration and selection of potential siRNAs with high accuracy and strength. This computational approach resulted in three effective siRNAs that can be taken further to in vivo animal studies and can be used to develop safe and effective antiviral therapies for other prevalent disease-causing viruses.


Subject(s)
Coronavirus Infections/therapy , Middle East Respiratory Syndrome Coronavirus/physiology , RNA, Small Interfering/pharmacology , RNAi Therapeutics , Virus Replication , Cell Line , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/genetics , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Viral Proteins/genetics , Virus Replication/drug effects
10.
Internet resource in Portuguese | LIS -Health Information Locator | ID: lis-48187

ABSTRACT

Este mapa de evidências apresenta uma síntese gráfica de estudos clínicos sobre a aplicação da Ozonioterapia em casos de COVID-19. A partir de uma ampla busca bibliográfica 11 estudos clínicos foram incluídos no mapa e categorizados por tipo de intervenção e por desfechos. Os estudos avaliaram o efeito de 4 tipos de intervenção com Ozonioterapia: auto-hemoterapia maior, auto-hemoterapia menor, insuflação retal e solução salina ozonizada; para 6 grupos de desfechos relacionados à COVID-19: Melhora clínica; Internação hospitalar; Marcadores inflamatórios, tromboembólicos, infecciosos ou metabólicos; Aspectos radiológicos; Infecção viral; e Eventos adversos. Principais Achados: Os estudos ocorreram no ano de 2020 nos seguintes países: Espanha (5 artigos), China (2 estudos), Itália (2 estudos), Índia (1 estudo) e Iraque (1 estudo); Os 11 estudos clínicos analisados envolveram um total de 259 pacientes com COVID-19 que receberam Ozonioterapia, todos os resultados foram positivos, tanto em pacientes com nível de gravidade leve a severa, sendo leve a moderada em 2 estudos, moderada a severa em 1 estudo, leve a severa em 1 estudo, moderada em 1 estudo, severa em 6 estudos; O tipo de intervenção mais relatado foi auto-hemoterapia maior, presente em 19 desfechos, seguido da insuflação retal, presente em 17 desfechos; Os desfechos relatados foram: melhora geral de sintomas clínicos de COVID-19 (11 estudos), redução do tempo de internação (6 estudos), diminuição da proteína C reativa (9 estudos), diminuição da ferritina (6 estudos), diminuição de lactato desidrogenase (7 estudos), diminuição do dímero-D (7 estudos), ausência ou inexistência de relato de eventos adversos (9 estudos); A concentração de ozônio medicinal na auto-hemoterapia maior variou de 20 a 45 mcg/mL, sendo 40 mcg/mL a concentração mais utilizada. Para a via de insuflação retal foi utilizada uma concentração de 35-40 mcg/mL, sendo a concentração de 35mcg/mL a mais utilizada.


Subject(s)
Coronavirus Infections/therapy , Insufflation/methods , Betacoronavirus , Saline Solution
11.
Medicine (Baltimore) ; 100(16): e25619, 2021 Apr 23.
Article in English | MEDLINE | ID: mdl-33879732

ABSTRACT

ABSTRACT: The coronavirus disease (COVID-19) outbreak was first reported in December 2019 in Wuhan, China. Specific information about critically ill COVID-19 patients receiving invasive mechanical ventilation (IMV) is rare.To describe the clinical course and complications of critically ill patients with COVID-19 who received IMV and were successfully weaned from it.This retrospective study included patients admitted to 3 intensive care units (ICUs) and 1 sub-ICU of Renmin Hospital of Wuhan University and Wuhan Jin Yin-tan Hospital between December 24, 2019, and March 12, 2020. Eleven patients who had been diagnosed with critically ill COVID-19 according to the World Health Organization interim guidance, received invasive ventilation, and were finally successfully weaned from it, were enrolled in our study. Their presenting symptoms, comorbidity conditions, laboratory values, ICU course, ventilator parameters, treatments, and relative complications were recorded.Of 108 critically ill COVID-19 patients who received invasive ventilation, 11 patients who underwent tracheal extubation or terminal weaning were included. The mean age of the 11 patients was 52.8 years (range, 38-70 years), 8 (72.7%) were male, and 2 were health care workers. The median time from onset of symptoms to dyspnea was 6.6 days (range, 3-13 days), and the median duration of IMV was 15.7 days (range, 6-29 days). All 11 patients presented with acute severe hypoxemic respiratory failure and received IMV, and 1 patient switched to extracorporeal membrane oxygenation assistance. A lung-protective strategy with lower tidal volume ventilation and proper driving pressure is the main strategy of IMV. All patients had extrapulmonary manifestations, including acute kidney injury, hepatic dysfunction, myocardial damage, and/or lymphopenia. Hospital-acquired infections occurred in 7 (63.6%) patients.Critical COVID-19 illness is characterized by acute hypoxemic respiratory failure and subsequent dysfunction of other organs with a high mortality rate. Correct ventilation strategies and other clinical strategies to improve oxygenation based on the skilled trained group and the availability of equipment are the key methods to rescue lives.


Subject(s)
Coronavirus Infections/therapy , Critical Care/methods , Respiration, Artificial , Ventilator Weaning , Adult , Aged , China , Coronavirus Infections/complications , Extracorporeal Membrane Oxygenation , Female , Humans , Hypoxia/therapy , Hypoxia/virology , Male , Middle Aged , Respiration, Artificial/adverse effects , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Retrospective Studies
12.
JMIR Public Health Surveill ; 7(4): e25500, 2021 04 07.
Article in English | MEDLINE | ID: mdl-33825689

ABSTRACT

BACKGROUND: The COVID-19 pandemic, caused by a novel coronavirus termed SARS-CoV-2, has spread quickly worldwide. Convalescent plasma (CP) obtained from patients following recovery from COVID-19 infection and development of antibodies against the virus is an attractive option for either prophylactic or therapeutic treatment, since antibodies may have direct or indirect antiviral activities and immunotherapy has proven effective in principle and in many clinical reports. OBJECTIVE: We seek to characterize the latest advances and evidence in the use of CP for COVID-19 through a systematic review and quantitative analysis, identify knowledge gaps in this setting, and offer recommendations and directives for future research. METHODS: PubMed, Web of Science, and Embase were continuously searched for studies assessing the use of CP for COVID-19, including clinical studies, commentaries, reviews, guidelines or protocols, and in vitro testing of CP antibodies. The screening process and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal of all clinical studies was conducted using a universal tool independent of study designs. A meta-analysis of case-control and randomized controlled trials (RCTs) was conducted using a random-effects model. RESULTS: Substantial literature has been published covering various aspects of CP therapy for COVID-19. Of the references included in this review, a total of 243 eligible studies including 64 clinical studies, 79 commentary articles, 46 reviews, 19 guidance and protocols, and 35 in vitro testing of CP antibodies matched the criteria. Positive results have been mostly observed so far when using CP for the treatment of COVID-19. There were remarkable heterogeneities in the CP therapy with respect to patient demographics, donor antibody titers, and time and dose of CP administration. The studies assessing the safety of CP treatment reported low incidence of adverse events. Most clinical studies, in particular case reports and case series, had poor quality. Only 1 RCT was of high quality. Randomized and nonrandomized data were found in 2 and 11 studies, respectively, and were included for meta-analysis, suggesting that CP could reduce mortality and increase viral clearance. Despite promising pilot studies, the benefits of CP treatment can only be clearly established through carefully designed RCTs. CONCLUSIONS: There is developing support for CP therapy, particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. These studies provide important lessons that should inform the planning of well-designed RCTs to generate more robust knowledge for the efficacy of CP in patients with COVID-19. Future research is necessary to fill the knowledge gap regarding prevention and treatment for patients with COVID-19 with CP while other therapeutics are being developed.


Subject(s)
COVID-19/therapy , Coronavirus Infections , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Humans , Immunization, Passive
13.
Acta Med Indones ; 53(1): 86-95, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33818411

ABSTRACT

The global widespread mortality after the emergence of SARS-CoV-2 infection in China, has become a critical concern all around the world. Convalescent plasma (CP) therapy is one of the methods elevating the survival rate for COVID-19 infection cases. This technique, as a practicable therapy, was used in previous viral outbreaks including influenza, SARS and MERS. In CP therapy, the blood plasma is collected from persons rehabilitated from that specific infection in order to develop a passive immunity in other patients. Therefore, this review aimed to point out the role of CP therapy in aforementioned viral infections and illustrate different factors influencing the efficacy of CP therapy.


Subject(s)
COVID-19/therapy , Coronavirus Infections/therapy , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/therapy , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/immunology , Humans , Immunization, Passive/methods , Treatment Outcome
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