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1.
Emerg Microbes Infect ; 13(1): 2359004, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38779718

RESUMO

As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Evasão da Resposta Imune , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , COVID-19/virologia , COVID-19/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Linhagem Celular , Mutação , Testes de Neutralização
2.
Open Forum Infect Dis ; 11(2): ofae039, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38328496

RESUMO

Background: The impact of vaccination prior to infection on postacute sequelae of coronavirus disease 2019 (COVID-19, PASC), also known as long COVID, remains unclear. Here we assess the protective effect of vaccination on long COVID in a community-based setting. Methods: The Immunity Associated with SARS-CoV-2 (IASO) study is an ongoing prospective cohort of working adults that began in October 2020. Participants are actively followed for severe acute respiratory syndrome coronavirus 2 infection. We compared the prevalence of symptoms and symptom severity in vaccinated compared to unvaccinated cases. Our primary definition of long COVID was the presence of symptoms at 90 days postinfection; 30 days postinfection was also examined. Results: Overall, by 90 days postinfection, 13% of cases had long COVID, with 27% of unvaccinated cases and 8% of vaccinated cases reporting long COVID (relative risk [RR], 0.31 [95% confidence interval {CI}, .22-.42]). Vaccination was also associated with significantly lower average severity scores at all timepoints (eg, relative severity at 90 days postinfection: -2.70 [95% CI, -1.68 to -3.73]). In the pre-Omicron era, 28% of unvaccinated cases and 18% of vaccinated cases reported long COVID (P = .07), and vaccinated cases reported less severe symptoms including less difficulty breathing (P = .01; 90-day RR, 0.07). Conclusions: Vaccinated cases had lower prevalence of long COVID and reduced symptom severity.

3.
JAMA ; 331(7): 611-612, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38252429

RESUMO

This JAMA Insights Clinical Update discusses the diagnosis, treatment, prognosis, and infection-prevention measures for Candida auris.


Assuntos
Candida auris , Candidíase , Humanos , Antifúngicos/uso terapêutico , Candida , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Testes de Sensibilidade Microbiana
6.
Am J Crit Care ; 31(6): 452-460, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35953441

RESUMO

BACKGROUND: Tracheostomies are highly aerosolizing procedures yet are often indicated in patients with COVID-19 who require prolonged intubation. Robust investigations of the safety of tracheostomy protocols and provider adherence and evaluations are limited. OBJECTIVES: To determine the rate of COVID-19 infection of health care personnel involved in COVID-19 tracheostomies under a multidisciplinary safety protocol and to investigate health care personnel's attitudes and suggested areas for improvement concerning the protocol. METHODS: All health care personnel involved in tracheostomies in COVID-19-positive patients from April 9 through July 11, 2020, were sent a 22-item electronic survey. RESULTS: Among 107 health care personnel (80.5%) who responded to the survey, 5 reported a positive COVID-19 test result (n = 2) or symptoms of COVID-19 (n = 3) within 21 days of the tracheostomy. Respondents reported 100% adherence to use of adequate personal protective equipment. Most (91%) were familiar with the tracheostomy protocol and felt safe (92%) while performing tracheostomy. Suggested improvements included creating dedicated tracheostomy teams and increasing provider choices surrounding personal protective equipment. CONCLUSIONS: Multidisciplinary engagement in the development and implementation of a COVID-19 tracheostomy protocol is associated with acceptable safety for all members of the care team.


Assuntos
COVID-19 , Humanos , Traqueostomia/efeitos adversos , SARS-CoV-2 , Equipamento de Proteção Individual , Atenção à Saúde
7.
Sci Transl Med ; 14(657): eabm4908, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35579540

RESUMO

The SARS-CoV-2 B.1.621 (Mu) variant emerged in January 2021 and was categorized as a variant of interest by the World Health Organization in August 2021. This designation prompted us to study the sensitivity of this variant to antibody neutralization. In a live virus neutralization assay with serum samples from individuals vaccinated with the Pfizer/BioNTech or Moderna mRNA vaccines, we measured neutralization antibody titers against B.1.621, an early isolate (spike 614D), and a variant of concern (B.1.351, Beta variant). We observed reduced neutralizing antibody titers against the B.1.621 variant (3.4- to 7-fold reduction, depending on the serum sample and time after the second vaccination) compared to the early isolate and a similar reduction when compared to B.1.351. Likewise, convalescent serum from hamsters previously infected with an early isolate neutralized B.1.621 to a lower degree. Despite this antibody titer reduction, hamsters could not be efficiently rechallenged with the B.1.621 variant, suggesting that the immune response to the first infection is adequate to provide protection against a subsequent infection with the B.1.621 variant.


Assuntos
COVID-19 , Proteínas do Envelope Viral , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/terapia , Humanos , Imunização Passiva , Glicoproteínas de Membrana/genética , Testes de Neutralização , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Proteínas do Envelope Viral/genética , Soroterapia para COVID-19
8.
Ann Thorac Surg ; 113(1): 118-124, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33662308

RESUMO

BACKGROUND: Infectious endocarditis is associated with substantial in-hospital mortality of 15%-20%. Effective management requires coordination between multiple medical and surgical subspecialties, which can often lead to disjointed care. Previous European studies have identified multidisciplinary endocarditis teams as a tool for reducing endocarditis mortality. METHODS: The multidisciplinary endocarditis team was formed in May 2018. The group developed an evidence-based algorithm for management of endocarditis that was used to provide recommendations for hospitalized patients over a 1-year period. Mortality outcomes were then retroactively assessed and compared to a historical control utilizing propensity matching. RESULTS: Between June 2018 and June 2019 the team provided guideline-based recommendations on 56 patients with Duke Criteria-definite endocarditis and at least 1 American Heart Association indication for surgery. The historical control included 68 patients with definite endocarditis and surgical indications admitted between July 1, 2014, and June 30, 2015. In-hospital mortality decreased significantly from 29.4% in 2014-2015 to 7.1% in 2018-2019 (P < .0001). There was a non-significant increase in the rate of surgical intervention after implementation of the team (41.2% vs 55.4%; P = 0.12). Propensity score matching demonstrated similar results. CONCLUSIONS: Implementation of a multidisciplinary endocarditis team was associated with a significant 1-year decrease in all-cause in-hospital mortality for patients with definite endocarditis and surgical indications, in the presence of notable differences between the 2 studied cohorts. In conjunction with previous studies demonstrating their effectiveness, these data support the idea that widespread adoption of endocarditis teams in North America could improve outcomes for this patient population.


Assuntos
Endocardite Bacteriana/cirurgia , Equipe de Assistência ao Paciente , Adulto , Idoso , Endocardite Bacteriana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão
9.
Ther Adv Infect Dis ; 8: 20499361211065596, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950478

RESUMO

Over the last several years multiple studies, primarily from European centers have demonstrated the clinical and outcomes benefits of multidisciplinary endocarditis teams. Despite this literature, adoption of this approach to patient care has been slower in the United States. While there is literature outlining the optimal composition of an endocarditis team, there is little information to guide providers as they attempt to transform practice from a fragmented, disjointed process to an efficient, collaborative care model. In this review, the authors will outline the steps they took to create and implement a successful multidisciplinary endocarditis team at the University of Michigan. In conjunction with existing data, this piece can be used as a resource for clinicians seeking to improve the care of patients with endocarditis at their institutions.

10.
J Am Board Fam Med ; 34(6): 1229-1242, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34772779

RESUMO

BACKGROUND: Post-COVID symptoms, defined as symptoms lasting >4 weeks postinfection, have been identified not only among those patients who were hospitalized with severe symptoms but also among those who were asymptomatic or with only mild symptoms. Primary care providers (PCPs) will often be the first point of contact for patients experiencing potential complications of post-COVID symptoms. The aim of this article is to present a post-COVID management tool for PCPs to use as a quick reference and guide to the initial workup and management of the most common post-COVID symptoms. METHODS: Published guidance, recent literature, and expert specialist opinion were used to create the structure outlining the outpatient evaluation and treatment for post-COVID symptoms. RESULTS: A quick-reference guide for management of post-COVID symptoms was created for PCPs. Educational materials were created for clinicians to share with patients. Our article reviews several common complaints including respiratory, cognitive, and neurological symptoms, chronic fatigue, dysautonomia, and anosmia and presents recommendations for management. CONCLUSIONS: Data on long-term effects of COVID-19 are still emerging, and rapid dissemination of this data to front-line PCPs is crucial. This table was our effort to make the currently available evidence accessible for our PCPs in a simple, easy-to-use format.


Assuntos
COVID-19 , Médicos de Atenção Primária , Humanos , SARS-CoV-2
11.
JMIR Res Protoc ; 10(5): e29562, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33945497

RESUMO

BACKGROUND: Health care workers (HCWs) have been working on the front lines of the COVID-19 pandemic with high risks of viral exposure, infection, and transmission. Standard COVID-19 testing is insufficient to protect HCWs from these risks and prevent the spread of disease. Continuous monitoring of physiological data with wearable sensors, self-monitoring of symptoms, and asymptomatic COVID-19 testing may aid in the early detection of COVID-19 in HCWs and may help reduce further transmission among HCWs, patients, and families. OBJECTIVE: By using wearable sensors, smartphone-based symptom logging, and biospecimens, this project aims to assist HCWs in self-monitoring COVID-19. METHODS: We conducted a prospective, longitudinal study of HCWs at a single institution. The study duration was 1 year, wherein participants were instructed on the continuous use of two wearable sensors (Fitbit Charge 3 smartwatch and TempTraq temperature patches) for up to 30 days. Participants consented to provide biospecimens (ie, nasal swabs, saliva swabs, and blood) for up to 1 year from study entry. Using a smartphone app called Roadmap 2.0, participants entered a daily mood score, submitted daily COVID-19 symptoms, and completed demographic and health-related quality of life surveys at study entry and 30 days later. Semistructured qualitative interviews were also conducted at the end of the 30-day period, following completion of daily mood and symptoms reporting as well as continuous wearable sensor use. RESULTS: A total of 226 HCWs were enrolled between April 28 and December 7, 2020. The last participant completed the 30-day study procedures on January 16, 2021. Data collection will continue through January 2023, and data analyses are ongoing. CONCLUSIONS: Using wearable sensors, smartphone-based symptom logging and survey completion, and biospecimen collections, this study will potentially provide data on the prevalence of COVID-19 infection among HCWs at a single institution. The study will also assess the feasibility of leveraging wearable sensors and self-monitoring of symptoms in an HCW population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04756869; https://clinicaltrials.gov/ct2/show/NCT04756869. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29562.

12.
Am J Transplant ; 21(8): 2885-2889, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33565705

RESUMO

We describe a case of proven transmission of SARS-CoV-2 from lung donor to recipient. The donor had no clinical history or findings suggestive of infection with SARS-CoV-2 and tested negative by reverse transcriptase polymerase chain reaction (RT-PCR) on a nasopharyngeal (NP) swab obtained within 48 h of procurement. Lower respiratory tract testing was not performed. The recipient developed fever, hypotension, and pulmonary infiltrates on posttransplant day (PTD) 3, and RT-PCR testing for SARS-CoV-2 on an NP swab specimen was non-reactive, but positive on bronchoalveolar lavage (BAL) fluid. One thoracic surgeon present during the transplantation procedure developed COVID-19. Sequence analysis of isolates from donor BAL fluid (obtained at procurement), the recipient, and the infected thoracic surgeon proved donor origin of recipient and health-care worker (HCW) infection. No other organs were procured from this donor. Transplant centers and organ procurement organizations should perform SARS-CoV-2 testing of lower respiratory tract specimens from potential lung donors, and consider enhanced personal protective equipment for HCWs involved in lung procurement and transplantation.


Assuntos
COVID-19 , Transplante de Pulmão , Teste para COVID-19 , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , SARS-CoV-2
13.
Int J Occup Environ Med ; 11(2): 65-71, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020915

RESUMO

The novel coronavirus (2019-nCoV) outbreak, which initially began in China, has spread to many countries around the globe, with the number of confirmed cases increasing every day. With a death toll exceeding that of the SARS-CoV outbreak back in 2002 and 2003 in China, 2019-nCoV has led to a public health emergency of international concern, putting all health organizations on high alert. Herein, we present on an overview of the currently available information on the pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of this virus.


Assuntos
Infecções por Coronavirus , Coronavirus , Surtos de Doenças/prevenção & controle , Pandemias , Pneumonia Viral , Animais , Betacoronavirus , COVID-19 , China/epidemiologia , Coronavirus/genética , Coronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Reservatórios de Doenças/virologia , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , SARS-CoV-2 , Zoonoses/epidemiologia , Zoonoses/prevenção & controle , Zoonoses/virologia
14.
J Virol ; 80(2): 671-81, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16378970

RESUMO

Mammalian reoviruses are internalized into cells by receptor-mediated endocytosis. Within the endocytic compartment, the viral outer capsid undergoes acid-dependent proteolysis resulting in removal of the sigma3 protein and proteolytic cleavage of the mu1/mu1C protein. Ammonium chloride (AC) is a weak base that blocks disassembly of reovirus virions by inhibiting acidification of intracellular vacuoles. To identify domains in reovirus proteins that influence pH-sensitive steps in viral disassembly, we adapted strain type 3 Dearing (T3D) to growth in murine L929 cells treated with AC. In comparison to wild-type (wt) T3D, AC-adapted (ACA-D) variant viruses exhibited increased yields in AC-treated cells. AC resistance of reassortant viruses generated from a cross of wt type 1 Lang and ACA-D variant ACA-D1 segregated with the sigma3-encoding S4 gene. The deduced sigma3 amino acid sequences of six independently derived ACA-D variants contain one or two mutations each, affecting a total of six residues. Four of these mutations, I180T, A246G, I347S, and Y354H, cluster in the virion-distal lobe of sigma3. Linkage of these mutations to AC resistance was confirmed in experiments using reovirus disassembly intermediates recoated with wt or mutant sigma3 proteins. In comparison to wt virions, ACA-D viruses displayed enhanced susceptibility to proteolysis by endocytic protease cathepsin L. Image reconstructions of cryoelectron micrographs of three ACA-D viruses that each contain a single mutation in the virion-distal lobe of sigma3 demonstrated native capsid protein organization and minimal alterations in sigma3 structure. These results suggest that mutations in sigma3 that confer resistance to inhibitors of vacuolar acidification identify a specific domain that regulates proteolytic disassembly.


Assuntos
Cloreto de Amônio/farmacologia , Proteínas do Capsídeo/genética , Reoviridae/fisiologia , Proteínas Virais/genética , Adaptação Fisiológica , Animais , Proteínas do Capsídeo/química , Catepsina L , Catepsinas/metabolismo , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Farmacorresistência Viral/genética , Células L/efeitos dos fármacos , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Reoviridae/química , Reoviridae/efeitos dos fármacos , Inoculações Seriadas , Proteínas Virais/química , Proteínas Virais Reguladoras e Acessórias , Montagem de Vírus
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