Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19: The TOGETHER Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine or lopinavir-ritonavir for the treatment of high-risk outpatients with COVID-19 in developing countries are needed. Objective: To determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting. Design, Setting, and Participants: This randomized clinical trial was conducted in Brazil. Recently symptomatic adults diagnosed with respiratory symptoms from SARS-CoV-2 infection were enrolled between June 2 and September 30, 2020. The planned sample size was 1476 patients, with interim analyses planned after 500 patients were enrolled. The trial was stopped after the interim analysis for futility with a sample size of 685 patients. Statistical analysis was performed in December 2020. Interventions: Patients were randomly assigned to hydroxychloroquine (800 mg loading dose, then 400 mg daily for 9 days), lopinavir-ritonavir (loading dose of 800 mg and 200 mg, respectively, every 12 hours followed by 400 mg and 100 mg, respectively, every 12 hours for the next 9 days), or placebo. Main Outcomes and Measures: The primary outcomes were COVID-19-associated hospitalization and death assessed at 90 days after randomization. COVID-19-associated hospitalization was analyzed with a Cox proportional hazards model. The trial included the following secondary outcomes: all-cause hospitalization, viral clearance, symptom resolution, and adverse events. Results: Of 685 participants, 632 (92.3%) self-identified as mixed-race, 377 (55.0%) were women, and the median (range) age was 53 (18-94) years. A total of 214 participants were randomized to hydroxychloroquine; 244, lopinavir-ritonavir; and 227, placebo. At first interim analysis, the data safety monitoring board recommended stopping enrollment of both hydroxychloroquine and lopinavir-ritonavir groups because of futility. The proportion of patients hospitalized for COVID-19 was 3.7% (8 participants) in the hydroxychloroquine group, 5.7% (14 participants) in the lopinavir-ritonavir group, and 4.8% (11 participants) in the placebo group. We found no significant differences between interventions for COVID-19-associated hospitalization (hydroxychloroquine: hazard ratio [HR], 0.76 [95% CI, 0.30-1.88]; lopinavir-ritonavir: HR, 1.16 [95% CI, 0.53-2.56] as well as for the secondary outcome of viral clearance through day 14 (hydroxychloroquine: odds ratio [OR], 0.91 [95% CI, 0.82-1.02]; lopinavir-ritonavir: OR, 1.04 [95% CI, 0.94-1.16]). At the end of the trial, there were 3 fatalities recorded, 1 in the placebo group and 2 in the lopinavir-ritonavir intervention group. Conclusions and Relevance: In this randomized clinical trial, neither hydroxychloroquine nor lopinavir-ritonavir showed any significant benefit for decreasing COVID-19-associated hospitalization or other secondary clinical outcomes. This trial suggests that expedient clinical trials can be implemented in low-income settings even during the COVID-19 pandemic. Trial Registration: ClinicalTrials.gov Identifier: NCT04403100.

Profile of natural killer cells after a previous natural Vaccinia virus infection in an in vitro viral re-exposure.

The present study compares the profile of NK cells in an in vitro re-exposure by Vaccinia virus (VACV), in groups that have had a previous vaccination or natural infection. Our data suggests that stimulation with VACV triggers a cytotoxic response by NK cells marked by an increase of NCRs: NKp30, NKp44, and NKp46 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. However, the degranulation and secretion processes are inhibited in infected (vaccinated and unvaccinated) subjects and in the non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. We demonstrated that stimulation with VACV downregulates the percentage of expression of Perforin, Granzyme A, and CD107a, but upregulate CD94 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. Furthermore, the percentage of IFN-γ(+) NK cells was significantly lower in non-infected unvaccinated subjects, when compared with infected (vaccinated and unvaccinated) and non-infected vaccinated individuals. Our results also show that the percentage of TNF-α(+) NK cells was significantly higher in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals, after in vitro stimulation with UV-inactivated VACV. Our data suggest that the expression of NCRs NKp30, NKp44, NKp46 and cytokines by NK cells are important in the innate response against VACV.

Clinical signs, diagnosis, and case reports of Vaccinia virus infections.

Vaccinia virus is responsible for a zoonosis that usually affects cattle and human beings in Brazil. The initial clinical signs of the infection are focal red skin areas, fever, and general symptoms similar to those of a cold. Then, pustules and ulcerated lesions surrounded by edema and erythema follow, as well as local lymphadenopathy that can last for weeks. Cure and healing of the lesions occur over several weeks, leaving a typical scar in the skin of people and animals affected. The infection definitive diagnosis is made through morphological characterization of the virus by use of electron microscopy, followed by PCR for specific viral genes. Since 1963, circulating orthopoxviruses in infectious outbreaks in several regions of Brazil have been reported. Later, the etiological agent of those infections was characterized as samples of Vaccinia virus. In addition, the widespread use of those viruses in research laboratories and mass vaccination of militaries have contributed to increase the cases of those infections worldwide. Thus, several epidemiological and clinical studies are required, as well as studies of viral immunology, public health, and economic impact, because little is known about those Vaccinia virus outbreaks in Brazil.

Clinical signs, diagnosis, and case reports of Vaccinia virus infections

Vaccinia virus is responsible for a zoonosis that usually affects cattle and human beings in Brazil. The initial clinical signs of the infection are focal red skin areas, fever, and general symptoms similar to those of a cold. Then, pustules and ulcerated lesions surrounded by edema and erythema follow, as well as local lymphadenopathy that can last for weeks. Cure and healing of the lesions occur over several weeks, leaving a typical scar in the skin of people and animals affected. The infection definitive diagnosis is made through morphological characterization of the virus by use of electron microscopy, followed by PCR for specific viral genes. Since 1963, circulating orthopoxviruses in infectious outbreaks in several regions of Brazil have been reported. Later, the etiological agent of those infections was characterized as samples of Vaccinia virus. In addition, the widespread use of those viruses in research laboratories and mass vaccination of militaries have contributed to increase the cases of those infections worldwide. Thus, several epidemiological and clinical studies are required, as well as studies of viral immunology, public health, and economic impact, because little is known about those Vaccinia virus outbreaks in Brazil.

Conhecimento das enfermeiras da Pós-Graduação em Saúde da Família sobre avulsão dentária / Nurses’ knowledge of the Postgraduate Program in Family’s Health on dental avulsion

Objetivos: investigar o conhecimento, as atitudes e práticas das enfermeiras alunas da especialização em Saúde daFamília do Instituto de Educação Continuada da PUC de Sete Lagoas sobre a avulsão dentária. Método: foi realizado umestudo transversal e descritivo. A população estudada constituiu-se de 17 enfermeiras, alunas do curso de Especializaçãoem Saúde da Família, que se voluntariaram a participar do estudo. Como instrumento para coleta de dados foi utilizadoum questionário adaptado, com perguntas acerca da temática avulsão dentária. Os dados obtidos foram submetidos aanálises quantitativas, através de métodos estatísticos descritivos. Resultados: a maioria das enfermeiras (71%) nuncaouviu falar de avulsão dentária. Cinco enfermeiras (29%) não saberiam quais as providências necessárias em caso deavulsão dentária, seis (35%) armazenariam o dente e encaminhariam a pessoa ao dentista, três (18%) apenasencaminhariam a pessoa ao dentista, uma enfermeira (6%) encaminharia a pessoa para fazer a restauração, uma aluna(6%) armazenaria o dente em leite e entregaria o dente ao socorrista, e apenas uma (6%) delas faria imediatamente oreimplante. Conclusões: pode-se afirmar que as enfermeiras analisadas não apresentaram conhecimentos sólidos quandoquestionadas acerca de diferentes aspectos de procedimentos em casos de tratamento de urgência por avulsão dentáriaocasional.

Processo de trabalho: sua importância na organização da prática assistencial de enfermagem na saúde coletiva / Work process: the importance in the organization of nursing assistant practices in collective health

Objetivo: analisar o processo de trabalho da enfermagem e discutir a importância do enfermeiro, em sua práticaassistencial, em desvelar o seu objeto e instrumentos de trabalho para então compreender o seu processo de trabalho e, asua real identidade profissional, com ênfase na saúde coletiva. Metodologia: pesquisa realizada na Biblioteca Regional deMedicina (BIREME), na qual foram obtidos 1741 artigos. Após, análise e síntese desses materiais foram selecionados 13artigos e, também foi realizada uma busca retroativa das referências dos artigos consultados a fim de ampliar as fontes depesquisa. Resultados: a partir dessa pesquisa, verificou-se que é crucial que a enfermagem se liberte desse velhoparadigma (biomédico, hegemônico) e, busque novas concepções que permitam alcançar autonomia e autogoverno doprofissional enfermeiro. Conclusão: o enfermeiro necessita clarificar as suas ferramentas de trabalho em sua práticaprofissional para que possa compreender o seu processo de trabalho.