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3.
Sci Rep ; 11(1): 14421, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257350

RESUMO

A plethora of measures are being combined in the attempt to reduce SARS-CoV-2 spread. Due to its sustainability, contact tracing is one of the most frequently applied interventions worldwide, albeit with mixed results. We evaluate the performance of digital contact tracing for different infection detection rates and response time delays. We also introduce and analyze a novel strategy we call contact prevention, which emits high exposure warnings to smartphone users according to Bluetooth-based contact counting. We model the effect of both strategies on transmission dynamics in SERIA, an agent-based simulation platform that implements population-dependent statistical distributions. Results show that contact prevention remains effective in scenarios with high diagnostic/response time delays and low infection detection rates, which greatly impair the effect of traditional contact tracing strategies. Contact prevention could play a significant role in pandemic mitigation, especially in developing countries where diagnostic and tracing capabilities are inadequate. Contact prevention could thus sustainably reduce the propagation of respiratory viruses while relying on available technology, respecting data privacy, and most importantly, promoting community-based awareness and social responsibility. Depending on infection detection and app adoption rates, applying a combination of digital contact tracing and contact prevention could reduce pandemic-related mortality by 20-56%.


Assuntos
COVID-19/prevenção & controle , Busca de Comunicante/métodos , Smartphone , Humanos , Pandemias/prevenção & controle , SARS-CoV-2/patogenicidade
4.
Sci Rep ; 11(1): 14390, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257394

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of disease than age-matched non-pregnant women, the risk of feto-placental infection is low. Using a cohort of 66 COVID-19-positive women in late pregnancy, we correlated clinical parameters with disease severity, placental histopathology, and the expression of viral entry and Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None of the demographic parameters or placental histopathological characteristics were associated with disease severity. The fetal-maternal transfer ratio for IgG against the N or S viral proteins was commonly less than one, as recently reported. We found that the expression level of placental ACE2, but not TMPRSS2 or Furin, was higher in women with severe COVID-19. Placental expression of IFITM1 and IFITM3, which have been implicated in antiviral response, was higher in participants with severe disease. We also showed that IFITM3 protein expression, which localized to early and late endosomes, was enhanced in severe COVID-19. Our data suggest an association between disease severity and placental SARS-CoV-2 processing and antiviral pathways, implying a role for these proteins in placental response to SARS-CoV-2.


Assuntos
COVID-19/metabolismo , Placenta/metabolismo , SARS-CoV-2/patogenicidade , Adulto , Enzima de Conversão de Angiotensina 2/metabolismo , Feminino , Furina/metabolismo , Humanos , Imunoglobulina G/metabolismo , Transmissão Vertical de Doenças Infecciosas , Masculino , Proteínas do Nucleocapsídeo/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/virologia , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Adulto Jovem
5.
Curr Allergy Asthma Rep ; 21(6): 38, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259961

RESUMO

PURPOSE OF REVIEW: Increasing knowledge of the pathogenesis of the SARS-CoV-2 infection and the complex interaction between host and viral factors have allowed clinicians to stratify the severity of COVID-19 infection. Epidemiological data has also helped to model viral carriage and infectivity. This review presents a comprehensive summary of the pathophysiology of COVID-19, the mechanisms of action of the SARS-CoV-2 virus, and the correlation with the clinical and biochemical characteristics of the disease. RECENT FINDINGS: ACE2 and TMPRSS2 receptors have emerged as a key player in the mechanism of infection of SARS-CoV-2. Their distribution throughout the body has been shown to impact the organ-specific manifestations of COVID-19. The immune-evasive and subsequently immunoregulative properties of SARS-CoV-2 are also shown to be implicated in disease proliferation and progression. Information gleaned from the virological properties of SARS-CoV-2 is consistent with and reflects the clinical behavior of the COVID-19 infection. Further study of specific clinical phenotypes and severity classes of COVID-19 may assist in the development of targeted therapeutics to halt progression of disease from mild to moderate-severe. As the understanding of the pathophysiology and mechanism of action of SARS-CoV-2 continues to grow, it is our hope that better and more effective treatment options continue to emerge.


Assuntos
COVID-19/fisiopatologia , SARS-CoV-2/patogenicidade , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Progressão da Doença , Humanos , Evasão da Resposta Imune , Especificidade de Órgãos , SARS-CoV-2/imunologia , Serina Endopeptidases/metabolismo , Índice de Gravidade de Doença , Internalização do Vírus
6.
Cells ; 10(7)2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201847

RESUMO

Cell death mechanisms are crucial to maintain an appropriate environment for the functionality of healthy cells. However, during viral infections, dysregulation of these processes can be present and can participate in the pathogenetic mechanisms of the disease. In this review, we describe some features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some immunopathogenic mechanisms characterizing the present coronavirus disease (COVID-19). Lymphopenia and monocytopenia are important contributors to COVID-19 immunopathogenesis. The fine mechanisms underlying these phenomena are still unknown, and several hypotheses have been raised, some of which assign a role to cell death as far as the reduction of specific types of immune cells is concerned. Thus, we discuss three major pathways such as apoptosis, necroptosis, and pyroptosis, and suggest that all of them likely occur simultaneously in COVID-19 patients. We describe that SARS-CoV-2 can have both a direct and an indirect role in inducing cell death. Indeed, on the one hand, cell death can be caused by the virus entry into cells, on the other, the excessive concentration of cytokines and chemokines, a process that is known as a COVID-19-related cytokine storm, exerts deleterious effects on circulating immune cells. However, the overall knowledge of these mechanisms is still scarce and further studies are needed to delineate new therapeutic strategies.


Assuntos
COVID-19/patologia , Morte Celular/fisiologia , SARS-CoV-2/patogenicidade , Apoptose/fisiologia , COVID-19/imunologia , COVID-19/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Citocinas/metabolismo , Humanos , Necroptose/fisiologia , Internalização do Vírus
8.
Rev Cardiovasc Med ; 22(2): 277-286, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258896

RESUMO

Emerging evidences prove that the ongoing pandemic of coronavirus disease 2019 (COVID-19) is strictly linked to coagulopathy even if pneumonia appears as the major clinical manifestation. The exact incidence of thromboembolic events is largely unknown, so that a relative significant number of studies have been performed in order to explore thrombotic risk in COVID-19 patients. Cytokine storm, mediated by pro-inflammatory interleukins, tumor necrosis factor α and elevated acute phase reactants, is primarily responsible for COVID-19-associated hypercoagulopathy. Also comorbidities, promoting endothelial dysfunction, contribute to a higher thromboembolic risk. In this review we aim to investigate epidemiology and clarify the pathophysiological pathways underlying hypercoagulability in COVID-19 patients, providing indications on the prevention of thromboembolic events in COVID-19. Furthermore we aim to reassume the pathophysiological paths involved in COVID-19 infection.


Assuntos
Coagulação Sanguínea , COVID-19/sangue , Embolia Pulmonar/sangue , Tromboembolia Venosa/sangue , Trombose Venosa/sangue , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Interações Hospedeiro-Patógeno , Humanos , Prognóstico , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/prevenção & controle , Embolia Pulmonar/virologia , Medição de Risco , Fatores de Risco , SARS-CoV-2/patogenicidade , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/virologia , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controle , Trombose Venosa/virologia
9.
Rev Cardiovasc Med ; 22(2): 315-327, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258900

RESUMO

There has been an apparent association between the risks of complications with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with a history of existing chronic respiratory diseases during the pandemic of coronavirus disease 2019 (COVID-19). SARS-CoV-2 poses a severe risk in cardiopulmonary management. Moreover, chronic respiratory diseases may further amplify the risk of morbidity and mortality among the afflicted population in the pandemic era. The present review outlines the importance of pulmonary rehabilitation (PR) in persons with chronic respiratory diseases (Chronic obstructive pulmonary disease (COPD) and Asthma) during the COVID-19 era. In this context, amongst the population with a pre-existing pulmonary diagnosis who have contracted SARS-CoV-2, following initial medical management and acute recovery, exercise-based pulmonary rehabilitation (PR) may play a crucial role in long-term management and recovery. The energy conservation techniques will play a pragmatic role in PR of mild to moderate severity cases to counter post-COVID-19 fatigue. Moreover, there is also an urgent need to effectively address post-COVID-19 anxiety and depression, affecting the PR delivery system.


Assuntos
Asma/reabilitação , COVID-19/terapia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Terapia Respiratória , Asma/fisiopatologia , COVID-19/fisiopatologia , COVID-19/virologia , Interações Hospedeiro-Patógeno , Humanos , Pulmão/virologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , SARS-CoV-2/patogenicidade , Fatores de Tempo , Resultado do Tratamento
10.
Rev Cardiovasc Med ; 22(2): 343-351, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258902

RESUMO

Coronavirus disease 2019 (COVID-19), a mystified cryptic virus has challenged the mankind that has brought life to a standstill. Catastrophic loss of life, perplexed healthcare system and the downfall of global economy are some of the outcomes of this pandemic. Humans are raging a war with an unknown enemy. Infections, irrespective of age and gender, and more so in comorbidities are escalating at an alarming rate. Cardiovascular diseases, are the leading cause of death globally with an estimate of 31% of deaths worldwide out of which nearly 85% are due to heart attacks and stroke. Theoretically and practically, researchers have observed that persons with pre-existing cardiovascular conditions are comparatively more vulnerable to the COVID-19 infection. Moreover, they have studied the data between less severe and more severe cases, survivors and non survivors, intensive care unit (ICU) patients and non ICU patients, to analyse the relationship and the influence of COVID-19 on cardiovascular health of an individual, further the risk of susceptibility to submit to the virus. This review aims to provide a comprehensive particular on the possible effects, either direct or indirect, of COVID-19 on the cardiovascular heath of an individual.


Assuntos
COVID-19/virologia , Doenças Cardiovasculares/virologia , Sistema Cardiovascular/virologia , SARS-CoV-2/patogenicidade , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/terapia , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Comorbidade , Interações Hospedeiro-Patógeno , Humanos , Prognóstico , Medição de Risco , Fatores de Risco , SARS-CoV-2/efeitos dos fármacos
11.
Rev Cardiovasc Med ; 22(2): 365-371, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258904

RESUMO

COVID-19 is a novel viral infection caused by severe acute respiratory syndrome (SARS) beta-coronavirus. Epidemiological status changes dynamically as the pandemy is far from ending. Several complications of presented virus may be similar to those observed in other viral infections. Despite lacking data, the heart involvement may be comparable to cardiac complications observed previously in those with SARS as well as Middle East Respiratory Syndrome (MERS). In COVID-19 we observe elevated levels of cardiac biomarkers, such as natriuretic peptides, troponins, myoglobin, C-reactive protein (CRP), interleukin-2 (IL-2), interleukin-6 (IL-6) and ferritin, which is likely the result of myocardial injury. The possible mechanisms of cardiovascular injury include direct toxicity through the viral invasion of cardiac myocytes, ACE-2 receptor-mediated CV (cardiac and endothelial) injury, microvascular dysfunction and thrombosis and cytokine release syndrome (mainly IL-6 mediated). Cardiac manifestations of COVID-19 are focal or global myocardial inflammation, necrosis, ventricular dysfunction, heart failure and arrhythmia.


Assuntos
COVID-19/virologia , Cardiopatias/virologia , Coração/virologia , SARS-CoV-2/patogenicidade , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/terapia , Coração/fisiopatologia , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Interações Hospedeiro-Patógeno , Humanos , Prognóstico , Fatores de Risco , SARS-CoV-2/efeitos dos fármacos
12.
J Clin Invest ; 131(13)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196300

RESUMO

BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).


Assuntos
COVID-19/sangue , COVID-19/virologia , SARS-CoV-2 , Viremia/sangue , Viremia/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Pandemias , Prognóstico , Proteoma/metabolismo , Proteômica , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Internalização do Vírus
13.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201415

RESUMO

The SARS-CoV-2 virus utilizes angiotensin converting enzyme (ACE-2) for cell entry and infection. This enzyme has important functions in the renin-angiotensin aldosterone system to preserve cardiovascular function. In addition to the heart, it is expressed in many tissues including the lung, intestines, brain, and kidney, however, its functions in these organs are mostly unknown. ACE-2 has membrane-bound and soluble forms. Its expression levels are altered in disease states and by a variety of medications. Currently, it is not clear how altered ACE-2 levels influence ACE-2 virulence and relevant complications. In addition, membrane-bound and soluble forms are thought to have different effects. Most work on this topic in the literature is on the SARS-CoV virus that has a high genetic resemblance to SARS-Co-V-2 and also uses ACE-2 enzyme to enter the cell, but with much lower affinity. More recent studies on SARS-CoV-2 are mainly clinical studies aiming at relating the effect of medications that are thought to influence ACE-2 levels, with COVID-19 outcomes for patients under these medications. This review paper aims to summarize what is known about the relationship between ACE-2 levels and SARS-CoV/SARS-CoV-2 virulence under altered ACE-2 expression states.


Assuntos
Enzima de Conversão de Angiotensina 2/fisiologia , COVID-19/fisiopatologia , COVID-19/virologia , SARS-CoV-2/patogenicidade , Enzima de Conversão de Angiotensina 2/química , Inibidores da Enzima Conversora de Angiotensina , Interações entre Hospedeiro e Microrganismos , Humanos , Pulmão/metabolismo , Virulência
14.
Dis Model Mech ; 14(6)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34219165

RESUMO

The COVID-19 pandemic has emphasised the need to develop effective treatments to combat emerging viruses. Model systems that poorly represent a virus' cellular environment, however, may impede research and waste resources. Collaborations between cell biologists and virologists have led to the rapid development of representative organoid model systems to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that lung organoids, in particular, have advanced our understanding of SARS-CoV-2 pathogenesis, and have laid a foundation to study future pandemic viruses and develop effective treatments.


Assuntos
COVID-19/virologia , Pulmão/virologia , Modelos Biológicos , Organoides/virologia , SARS-CoV-2 , Animais , COVID-19/epidemiologia , Humanos , Pandemias , Alvéolos Pulmonares/virologia , Projetos de Pesquisa/tendências , SARS-CoV-2/patogenicidade
15.
Viruses ; 13(6)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203647

RESUMO

Influenza is a highly known contagious viral infection that has been responsible for the death of many people in history with pandemics. These pandemics have been occurring every 10 to 30 years in the last century. The most recent global pandemic prior to COVID-19 was the 2009 influenza A (H1N1) pandemic. A decade ago, the H1N1 virus caused 12,500 deaths in just 19 months globally. Now, again, the world has been challenged with another pandemic. Since December 2019, the first case of a novel coronavirus (COVID-19) infection was detected in Wuhan. This infection has risen rapidly throughout the world; even the World Health Organization (WHO) announced COVID-19 as a worldwide emergency to ensure human health and public safety. This review article aims to discuss important issues relating to COVID-19, including clinical, epidemiological, and pathological features of COVID-19 and recent progress in diagnosis and treatment approaches for the COVID-19 infection. We also highlight key similarities and differences between COVID-19 and influenza A to ensure the theoretical and practical details of COVID-19.


Assuntos
COVID-19/epidemiologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/epidemiologia , SARS-CoV-2/patogenicidade , Saúde Global , Humanos , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Organização Mundial da Saúde
16.
Viruses ; 13(6)2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207152

RESUMO

This article reviews the current knowledge on how viruses may utilize Extracellular Vesicle Assisted Inflammatory Load (EVAIL) to exert pathologic activities. Viruses are classically considered to exert their pathologic actions through acute or chronic infection followed by the host response. This host response causes the release of cytokines leading to vascular endothelial cell dysfunction and cardiovascular complications. However, viruses may employ an alternative pathway to soluble cytokine-induced pathologies-by initiating the release of extracellular vesicles (EVs), including exosomes. The best-understood example of this alternative pathway is human immunodeficiency virus (HIV)-elicited EVs and their propensity to harm vascular endothelial cells. Specifically, an HIV-encoded accessory protein called the "negative factor" (Nef) was demonstrated in EVs from the body fluids of HIV patients on successful combined antiretroviral therapy (ART); it was also demonstrated to be sufficient in inducing endothelial and cardiovascular dysfunction. This review will highlight HIV-Nef as an example of how HIV can produce EVs loaded with proinflammatory cargo to disseminate cardiovascular pathologies. It will further discuss whether EV production can explain SARS-CoV-2-mediated pulmonary and cardiovascular pathologies.


Assuntos
Vesículas Extracelulares/imunologia , Vesículas Extracelulares/virologia , Inflamação/virologia , COVID-19/complicações , COVID-19/imunologia , COVID-19/fisiopatologia , Doenças Cardiovasculares/virologia , Células Endoteliais/patologia , Células Endoteliais/virologia , Exossomos/metabolismo , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , HIV-1/patogenicidade , Humanos , SARS-CoV-2/patogenicidade
17.
Viruses ; 13(6)2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208484

RESUMO

Pets play a crucial role in the development of human feelings, social life, and care. However, in the era of the prevailing global pandemic of COVID-19 disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many questions addressing the routes of the virus spread and transmission to humans are dramatically emerging. Although cases of SARS-CoV-2 infection have been found in pets including dogs, cats, and ferrets, to date there is no strong evidence for pet-to-human transmission or sustained pet-to-pet transmission of SARS-CoV-2. However, an increasing number of studies reporting detection of SARS-CoV-2 in farmed minks raises suspicion of potential viral transmission from these animals to humans. Furthermore, due to the high susceptibility of cats, ferrets, minks and hamsters to COVID-19 infection under natural and/or experimental conditions, these animals have been extensively explored as animal models to study the SARS-CoV-2 pathogenesis and transmission. In this review, we present the latest reports focusing on SARS-CoV-2 detection, isolation, and characterization in pets. Moreover, based on the current literature, we document studies aiming to broaden the knowledge about pathogenicity and transmissibility of SARS-CoV-2, and the development of viral therapeutics, drugs and vaccines. Lastly, considering the high rate of SARS-CoV-2 evolution and replication, we also suggest routes of protection against the virus.


Assuntos
COVID-19/transmissão , Animais de Estimação/virologia , SARS-CoV-2/patogenicidade , Zoonoses/transmissão , Zoonoses/virologia , Animais , COVID-19/prevenção & controle , Gatos/virologia , Cães/virologia , Fazendas , Furões/virologia , Humanos , Vison/virologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação
18.
Eur Rev Med Pharmacol Sci ; 25(12): 4405-4412, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34227076

RESUMO

SARS-CoV-2 are enveloped RNA viruses that belong to the family Coronaviridae of genus Beta coronavirus, responsible for the COVID-19 pandemic. The mutation rate is high among RNA viruses and in particular, coronavirus replication is error prone with an estimated mutation rate of 4x10-4 nucleotide substitutions per site per year. Variants of SARS-CoV-2 have been reported from various countries like United Kingdom, South Africa, Denmark, Brazil and India. These variants evolved due to mutations in spike gene of SARS-CoV-2. The most concerning variants are Variant of Concern (VOC) 202012/01 from United Kingdom and B.1.617 variant of India. Other variants include B.1.351 lineages, cluster 5/SARS-CoV-2 variant of Denmark, 501.V2 variant/SARS-CoV-2 variant of South Africa, lineage B.1.1.248/lineage P.1 of Brazil. Mutations in S protein may result in changes in the transmissibility and virulence of SARS-CoV-2. To date, alterations in virulence or pathogenicity have been reported among the variants from many parts of the globe. In our opinion, since the S protein is significantly altered, the suitability of existing vaccine specifically targeting the S protein of SARS-CoV-2 variants is a major concern. The mutations in SARS-CoV-2 are a continuous and evolving process that may result in the transformation of naïve SARS-CoV-2 into totally new subsets of antigenically different SARS-CoV-2 viruses over a period of time.


Assuntos
COVID-19/epidemiologia , COVID-19/genética , Mutação/genética , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , COVID-19/transmissão , Humanos , Índia/epidemiologia , Estrutura Secundária de Proteína , SARS-CoV-2/química , Reino Unido/epidemiologia , Virulência/genética
20.
Respir Res ; 22(1): 200, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233672

RESUMO

BACKGROUND: The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics. METHODS: Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS-), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays. RESULTS: As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. CONCLUSION: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.


Assuntos
Corticosteroides/administração & dosagem , Enzima de Conversão de Angiotensina 2/metabolismo , Asma/tratamento farmacológico , Receptores Virais/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Administração por Inalação , Corticosteroides/efeitos adversos , Adulto , Enzima de Conversão de Angiotensina 2/genética , Asma/diagnóstico , Asma/enzimologia , Asma/genética , COVID-19/enzimologia , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Virais/genética , Mucosa Respiratória/enzimologia , SARS-CoV-2/patogenicidade , Fatores de Tempo , Regulação para Cima , Internalização do Vírus , Adulto Jovem
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