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1.
Exp Clin Transplant ; 18(3): 270-274, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32519617

RESUMO

OBJECTIVES: The novel 2019 coronavirus (COVID-19) was first described in December 2019 in Wuhan, China and subsequently announced as a pandemic on March 12, 2020. In several studies, solid-organ transplant recipients were reported to have higher risk for COVID-19. Here, we aimed to determine the frequency of COVID-19 in our kidney and liver transplant patients. MATERIALS AND METHODS: Our study included 583 transplant patients who were admitted to our outpatient transplant clinics and emergency departments between March 1 and May 1, 2020. Seventy-four of them were liver transplant recipients (46 male, 28 female, of which 14 were pediatric and 60 were adult patients) and 509 of them were kidney transplant recipients (347 male, 162 female, of which 16 were pediatric and 493 were adult patients). We retrospectively evaluated demographic characteristics, currently used immunosuppressant treatment, present complaints, treatment and diagnosis of comorbid diseases, and results of COVID-19 tests. RESULTS: Of 583 transplant recipients, 538 were seen in our outpatient transplant clinics and 45 were seen in our emergency departments. Of these, 18 patients who had had cough and fever were evaluated by respiratory clinic doctors, and nasopharyngeal swab samples were taken. One kidney transplant recipient had a positive COVID-19 test; he was followed with home isolation. He received treatment with hydroxychloroquine (400 mg/day). The other 17 patients had negative tests. There were no mortalities due to COVID-19. CONCLUSIONS: Transplant patients also got affected during the COVID-19 pandemic. According to the data of our centers, this effect is not much more different from the normal population. We recommend that transplant recipients should be warned in terms of personal hygiene and should be closely monitored by organ transplant centers. If there is an indication for hospitalization, they should be followed in an isolated unit, with no aggressive changes made to immunosuppressive doses unless necessary.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Infecções Oportunistas/epidemiologia , Pneumonia Viral/epidemiologia , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imunossupressores/efeitos adversos , Masculino , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Turquia/epidemiologia
2.
Exp Clin Transplant ; 18(3): 275-283, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32519618

RESUMO

OBJECTIVES: COVID-19 is a great threat to the modern world and significant threat to immunocompromised patients, including patients with chronic renal failure. We evaluated COVID-19 incidence among our hemodialysis patients and investigated the most probable immune mechanisms against COVID-19. MATERIALS AND METHODS: Baskent University has 21 dialysis centers across Turkey, with 2420 patients on hemodialysis and 30 on peritoneal dialysis. Among these, we retrospectively evaluated 602 patients (257 female/345 male) with chronic renal failure receiving hemodialysis as renal replacement therapy; 7 patients (1.1%) were infected with SARS-CoV-2. We retrospectively collected patient demographic characteristics, clinical data, and immunological factors affecting the clinical course of the disease. We divided patients into groups and included 2 control groups (individuals with normal renal functions): group I included COVID-19-positive patients with normal renal function, group II included COVID-19-positive hemodialysis patients, group III included COVID-19-negative hemodialysis patients, and group IV included COVID-19-negative patients with normal renal function. Lymphocyte subsets in peripheral blood and typing of human leukocyte antigens were analyzed in all groups, with killer cell immunoglobulin like receptor genes analyzed only in COVID-19-positive patients and healthy controls. RESULTS: No deaths occurred among the 7 COVID-19-positive hemodialysis patients. Group I patients were significantly older than patients in groups II and III (P = .039, P = .030, respectively) but not significantly different from group IV (P = .060). Absolute counts of natural killer cells in healthy controls were higherthan in other groups (but not significantly). ActivatedT cells were significantly increased in both COVID-19-positive groups versus COVID-19-negative groups. Groups showed significant differences in C and DQ loci with respect to distribution of alleles in both HLA classes. CONCLUSIONS: Although immunocompromised patients are at greater risk for COVID-19, we found lower COVID-19 incidence in our hemodialysis patients, which should be further investigated in in vitro and molecular studies.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Hospedeiro Imunocomprometido , Falência Renal Crônica/terapia , Infecções Oportunistas/epidemiologia , Pneumonia Viral/epidemiologia , Diálise Renal/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Linfócitos T/imunologia , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
5.
Immunobiology ; 225(3): 151955, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32517882

RESUMO

SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus. So far, the pandemic has caused the death of hundreds of thousands of people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. Therefore, this study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation, three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against the SARS-CoV-2. Thereafter, the molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive preventative measure against this lethal disease.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Proteínas Virais/química , Vacinas Virais/biossíntese , Sequência de Aminoácidos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Biologia Computacional/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Progressão da Doença , Epitopos/química , Epitopos/imunologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Plasmídeos/química , Plasmídeos/imunologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Conformação Proteica , Genética Reversa/métodos , Alinhamento de Sequência , Vacinas de Subunidades , Proteínas Virais/genética , Proteínas Virais/imunologia
8.
Rev Med Interne ; 41(6): 375-389, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32507520

RESUMO

SARS-CoV-2 infection, named COVID-19, can lead to a dysregulated immune response and abnormal coagulation responsible for a viral sepsis. In this review, we specify physiopathological mechanisms of each phase of COVID-19 - viral, immune and pro-thrombotic - notably because they involve different treatment. Finally, we specify the physiopathological mechanisms of organ injury.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Animais , Betacoronavirus/genética , Betacoronavirus/imunologia , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Citocinas/metabolismo , Humanos , Imunização , Imunomodulação , Especificidade de Órgãos , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Trombose/prevenção & controle , Trombose/virologia , Tropismo Viral , Internalização do Vírus , Replicação Viral/fisiologia , Zoonoses/virologia
9.
Pathog Dis ; 78(3)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32510562

RESUMO

Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50-66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Imunidade Coletiva , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Tempo
10.
Chiropr Man Therap ; 28(1): 34, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517803

RESUMO

BACKGROUND: Social media has become an increasingly important tool in monitoring the onset and spread of infectious diseases globally as well monitoring the spread of information about those diseases. This includes the spread of misinformation, which has been documented within the context of the emerging COVID-19 crisis. Understanding the creation, spread and uptake of social media misinformation is of critical importance to public safety. In this descriptive study, we detail Twitter activity regarding spinal manipulative therapy (SMT) and claims it increases, or "boosts", immunity. Spinal manipulation is a common intervention used by many health professions, most commonly by chiropractors. There is no clinical evidence that SMT improves human immunity. METHODS: Social media searching software (Talkwalker Quick Search) was used to describe Twitter activity regarding SMT and improving or boosting immunity. Searches were performed for the 3 months and 12 months before March 31, 2020 using terms related to 1) SMT, 2) the professions that most often provide SMT and 3) immunity. From these searches, we determined the magnitude and time course of Twitter activity then coded this activity into content that promoted or refuted a SMT/immunity link. Content themes, high-influence users and user demographics were then stratified as either promoting or refuting this linkage. RESULTS: Twitter misinformation regarding a SMT/immunity link increased dramatically during the onset of the COVID crisis. Activity levels (number of tweets) and engagement scores (likes + retweets) were roughly equal between content promoting or refuting a SMT/immunity link, however, the potential reach (audience) of tweets refuting a SMT/immunity link was 3 times higher than those promoting a link. Users with the greatest influence on Twitter, as either promoters or refuters, were individuals, not institutions or organizations. The majority of tweets promoting a SMT/immunity link were generated in the USA while the majority of refuting tweets originated from Canada. CONCLUSION: Twitter activity about SMT and immunity increased during the COVID-19 crisis. Results from this work have the potential to help policy makers and others understand the impact of SMT misinformation and devise strategies to mitigate its impact.


Assuntos
Betacoronavirus/imunologia , Comunicação , Infecções por Coronavirus/imunologia , Imunidade/fisiologia , Manipulação da Coluna , Pneumonia Viral/imunologia , Mídias Sociais/estatística & dados numéricos , Humanos , Pandemias , Mídias Sociais/normas , Fatores de Tempo
11.
Artigo em Inglês | MEDLINE | ID: mdl-32518172

RESUMO

OBJECTIVE: To present the COVID-19-associated GBS, the prototypic viral-triggered autoimmune disease, in the context of other emerging COVID-19-triggered autoimmunities, and discuss potential concerns with ongoing neuroimmunotherapies. METHODS: Eleven GBS cases in four key COVID-19 hotspots are discussed regarding presenting symptoms, response to therapies and cross-reactivity of COVID spike proteins with nerve glycolipids. Emerging cases of COVID-19-triggered autoimmune necrotizing myositis (NAM) and encephalopathies are also reviewed in the context of viral invasion, autoimmunity and ongoing immunotherapies. RESULTS: Collective data indicate that in this pandemic any patient presenting with an acute paralytic disease-like GBS, encephalomyelitis or myositis-even without systemic symptoms, may represent the first manifestation of COVID-19. Anosmia, ageusia, other cranial neuropathies and lymphocytopenia are red flags enhancing early diagnostic suspicion. In Miller-Fisher Syndrome, ganglioside antibodies against GD1b, instead of QG1b, were found; because the COVID-19 spike protein also binds to sialic acid-containing glycoproteins for cell-entry and anti-GD1b antibodies typically cause ataxic neuropathy, cross-reactivity between COVID-19-bearing gangliosides and peripheral nerve glycolipids was addressed. Elevated Creatine Kinase (>10,000) is reported in 10% of COVID-19-infected patients; two such patients presented with painful muscle weakness responding to IVIg indicating that COVID-19-triggered NAM is an overlooked entity. Cases of acute necrotizing brainstem encephalitis, cranial neuropathies with leptomeningeal enhancement, and tumefactive postgadolinium-enhanced demyelinating lesions are now emerging with the need to explore neuroinvasion and autoimmunity. Concerns for modifications-if any-of chronic immunotherapies with steroids, mycophenolate, azathioprine, IVIg, and anti-B-cell agents were addressed; the role of complement in innate immunity to viral responses and anti-complement therapeutics (i.e. eculizumab) were reviewed. CONCLUSIONS: Emerging data indicate that COVID-19 can trigger not only GBS but other autoimmune neurological diseases necessitating vigilance for early diagnosis and therapy initiation. Although COVID-19 infection, like most other viruses, can potentially worsen patients with pre-existing autoimmunity, there is no evidence that patients with autoimmune neurological diseases stable on common immunotherapies are facing increased risks of infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Miosite/diagnóstico , Miosite/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/etiologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Feminino , Síndrome de Guillain-Barré/imunologia , Humanos , Masculino , Miosite/imunologia , Pandemias , Pneumonia Viral/imunologia
13.
Gulf J Oncolog ; 1(33): 7-18, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476644

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. In December 2019, an outbreak of atypical pneumonia known as COVID-19 was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), is characterized by rapid human-to-human transmission. Acute lymphoblastic leukemia (ALL) patients are often in need for intensive chemotherapy to induce remission that will be complicated with prolonged period of cytopenias. They are often recalled to the hospital for treatment and disease surveillance. These patients may be immunocompromised due to the underlying malignancy or anti-cancer therapy. ALL patients are at higher risk of developing life-threatening infections. Several factors increase the risk of infection and the presence of multiple risk factors in the same patient is common. Cancer patients had an estimated 2-fold increased risk of contracting SARS-CoV-2 than the general population. With the World Health Organization declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such pandemic on ALL patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the optimal management of ALL patients in any infectious pandemic. In this review, we will address the potential challenges associated with managing ALL patients during the COVID-19 infection pandemic with suggestions of some practical approaches, focusing on screening asymptomatic ALL patients, diagnostic and response evaluation and choice of chemotherapy in different scenarios and setting and use of hematopoietic stem cell transplantation (HSCT).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Infecções Oportunistas/virologia , Pneumonia Viral/virologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Betacoronavirus/imunologia , Tomada de Decisão Clínica , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Procedimentos Clínicos , Técnicas de Apoio para a Decisão , Humanos , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/transmissão , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Medição de Risco , Fatores de Risco
14.
Cien Saude Colet ; 25(suppl 1): 2395-2401, 2020 Jun.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32520284

RESUMO

COVID-19, the disease produced by the virus SARS-CoV-2, has spread quickly throughout the world, leading the World Health Organization to first classify it as an international health emergency and, subsequently, declaring it pandemic. The number of confirmed cases, as April 11, surpassed 1,700,000, but this figure does not reflect the prevalence of COVID-19 in the population as, in many countries, tests are almost exclusively performed in people with symptoms, particularly severe cases. To properly assess the magnitude of the problem and to contribute to the design of evidence-based policies for fighting COVID-19, one must accurately estimate the population prevalence of infection. Our study is aimed at estimating the prevalence of infected individuals in the state of Rio Grande do Sul, Brazil, to document how fast the infection spreads, and to estimate the proportion of infected persons who present or presented symptoms, as well as the proportion of asymptomatic infections. Four repeated serological surveys will be conducted in probability samples of nine sentinel cities every two weeks. Tests will be performed in 4,500 participants in each survey, totaling18,000 interviews. Interviews and tests will be conducted at the participants' household. A rapid test for the detection of antibodies will be used; the test was validated prior to the beginning of the fieldwork.


Assuntos
Infecções Assintomáticas/epidemiologia , Betacoronavirus , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Vigilância de Evento Sentinela , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Brasil/epidemiologia , Técnicas de Laboratório Clínico/ética , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Humanos , Pneumonia Viral/transmissão , Prevalência , Fatores de Tempo
15.
BMJ ; 369: m2094, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493739

RESUMO

OBJECTIVES: To describe the characteristics of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to evaluate a potential temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: General paediatric department of a university hospital in Paris, France. PARTICIPANTS: 21 children and adolescents (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020. MAIN OUTCOME MEASURES: The primary outcomes were clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus. RESULTS: 21 children and adolescents (median age 7.9 (range 3.7-16.6) years) were admitted with features of Kawasaki disease over a 15 day period, with 12 (57%) of African ancestry. 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms during the early stage of illness and high levels of inflammatory markers. 19 (90%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By 15 May 2020, after 8 (5-17) days of hospital stay, all patients were discharged home. CONCLUSIONS: The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Adolescente , Corticosteroides/uso terapêutico , Betacoronavirus/genética , Betacoronavirus/imunologia , Criança , Pré-Escolar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Nasofaringe/virologia , Pandemias , Paris , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Estudos Prospectivos , RNA Viral/genética , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/etiologia
16.
ACS Nano ; 14(6): 6383-6406, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32519842

RESUMO

The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of "nanoimmunity by design" can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/genética , Betacoronavirus/imunologia , Biomimética , Simulação por Computador , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Desinfecção , Sistemas de Liberação de Medicamentos , Microbiologia Ambiental , Humanos , Imunomodulação , Máscaras , Nanomedicina , Nanotecnologia/tendências , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Fotoquimioterapia , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Vacinas Virais/genética , Vacinas Virais/farmacologia
17.
Trials ; 21(1): 499, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513308

RESUMO

OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection. TRIAL DESIGN: This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor. PARTICIPANTS: Eligible participants include adults (≥ 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) for ≥ 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion. *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA. INTERVENTION AND COMPARATOR: The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 - 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 - 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis. MAIN OUTCOMES: The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period. RANDOMIZATION: Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability. BLINDING (MASKING): The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5. TRIAL STATUS: Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Ensaios Clínicos Fase II como Assunto , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Pandemias , Estudos Prospectivos
18.
MMWR Morb Mortal Wkly Rep ; 69(23): 714-721, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32525850

RESUMO

Compared with the volume of data on coronavirus disease 2019 (COVID-19) outbreaks among older adults, relatively few data are available concerning COVID-19 in younger, healthy persons in the United States (1,2). In late March 2020, the aircraft carrier USS Theodore Roosevelt arrived at port in Guam after numerous U.S. service members onboard developed COVID-19. In April, the U.S. Navy and CDC investigated this outbreak, and the demographic, epidemiologic, and laboratory findings among a convenience sample of 382 service members serving aboard the aircraft carrier are reported in this study. The outbreak was characterized by widespread transmission with relatively mild symptoms and asymptomatic infection among this sample of mostly young, healthy adults with close, congregate exposures. Service members who reported taking preventive measures had a lower infection rate than did those who did not report taking these measures (e.g., wearing a face covering, 55.8% versus 80.8%; avoiding common areas, 53.8% versus 67.5%; and observing social distancing, 54.7% versus 70.0%, respectively). The presence of neutralizing antibodies, which represent antibodies that inhibit SARS-CoV-2, among the majority (59.2%) of those with antibody responses is a promising indicator of at least short-term immunity. This report improves the understanding of COVID-19 in the U.S. military and among young adults in congregate settings and reinforces the importance of preventive measures to lower risk for infection in similar environments.


Assuntos
Aeronaves , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Surtos de Doenças , Militares/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pandemias , Estados Unidos/epidemiologia , Adulto Jovem
19.
Sci Immunol ; 5(48)2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527802

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.


Assuntos
Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Epitopos Imunodominantes/imunologia , Pneumonia Viral/diagnóstico , Domínios Proteicos/imunologia , Glicoproteína da Espícula de Coronavírus/química , Zoonoses/sangue , Animais , Anticorpos Monoclonais , Anticorpos Neutralizantes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Humanos , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Ligação Proteica , Coelhos , Vírus da SARS/química , Vírus da SARS/imunologia , Testes Sorológicos , Zoonoses/virologia
20.
Viruses ; 12(6)2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532085

RESUMO

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-ß1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Animais , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Betacoronavirus/metabolismo , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Humanos , Interferons/metabolismo , Lipogênese/efeitos dos fármacos , Pandemias , Pneumonia Viral/virologia , Transdução de Sinais/efeitos dos fármacos , Células Vero , Carga Viral/efeitos dos fármacos , Ensaio de Placa Viral , Replicação Viral/efeitos dos fármacos
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