Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic

Abstract We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients.

Impact of lockdown during COVID-19 pandemic on physical activity and arrhythmia burden in heart failure patients.

BACKGROUND: Restricted outdoor activity during COVID-19 related lockdown may accelerate heart failure (HF) progression and thereby increase cardiac arrhythmias. We analyzed the impact of March/April 2020 lockdown on physical activity and arrhythmia burden in HF patients treated with cardiac resynchronization therapy (CRT) devices with daily, automatic remote monitoring (RM) function. METHODS: The study cohort included 405 HF patients enrolled in Observation of Clinical Routine Care for Heart Failure Patients Implanted with BIOTRONIK CRT Devices (BIO|STREAM.HF) registry in 16 countries, who had left ventricular ejection fraction (LVEF) ≤40% (mean 28.2 ± 6.6%) and NYHA class II/III/IV (47.9%/49.6%/2.5%) before CRT pacemaker/defibrillator implantation. The analyzed RM data comprised physical activity detected by accelerometer, mean heart rate and nocturnal rate, PP variability, percentage of biventricular pacing, atrial high rate episode (AHRE) burden, ventricular extrasystoles and tachyarrhythmias, defibrillator shocks, and number of implant interrogations (i.e., follow-ups). Intraindividual differences in RM parameters before (4-week period) versus during (4-week period) lockdown were tested for statistical significance and independent predictors were identified. RESULTS: There was a significant relative change in activity (mean -6.5%, p < .001), AHRE burden (+17%, p = .013), and follow-up rate (-75%, p < .001) during lockdown, with no significant changes in other RM parameters. Activity decreased by ≥8 min/day in 46.5% of patients; predictors were higher LVEF, lower NYHA class, no defibrillator indication, and more activity before lockdown. AHRE burden increased by ≥17 min/day in 4.7% of patients; predictors were history of atrial fibrillation, higher LVEF, higher body mass index, and activity decrease during lockdown. CONCLUSION: Unfavorable changes in physical activity, AHRE burden, and follow-up rate were observed during lockdown, but not in ventricular arrhythmia.

[Modelling the Contribution of Factors Influencing the Risk of SARS-CoV-2 Infection in Indoor Environments].

INTRODUCTION: This study estimates the risk of aerosol infection by SARS-CoV-2 in indoor environments where high density of occupation results in an increased probability of infection, such as schools, offices, supermarkets, restaurants and gyms. MATERIAL AND METHODS: In each type of building use, several conditions were simulated, such as the use and effectiveness of masks, ventilation, use of equipment that allows air asepsis using HEPA filters, the density of occupancy and the length of stay in the spaces, using a model based on the dispersion of aerosol particles in indoor spaces and on the accumulation and inhalation of these particles over time. RESULTS: The results showed that the replacement of social masks by masks with FFP2 classification decreased the risk of infection by 90% in schools. In schools with natural ventilation, the complete opening of windows reduced the risk of infection by 64% in comparison with the scenario with closed windows. In spaces where mechanical ventilation is normally used, the probability of infection decreased significantly when the regulatory fresh air flow rates were doubled (reduction of 32% in offices, 42% in restaurants, 24% in supermarkets and 46% in gyms). The filtration of air with HEPA filters allowed the reduction of the probability of infection by 72% in schools, offices, and restaurants and 61% in gyms. The length of stay in the spaces was also a relevant factor in the variation of the probability of infection, especially in schools where it was found that shorter classes with a higher number of intervals reduced the risk of infection. DISCUSSION: The results show the importance of adequate ventilation in indoor environments, especially in places where the density of occupation and the staying times are longer, making the introduction of outside air inside the spaces essential, either through natural or mechanical means. It is expected that the infection risk estimates presented are undervalued because the model only considers transmission by particles smaller than 10 µm and does not include the short-range transmission by assuming social distancing. Vaccination was not considered in the model since it was not yet available when the study was carried out. CONCLUSION: The present study contributes to the identification of measures that decrease the risk of viral transmission, and consequently provide greater security in indoor spaces.

Introdução: O presente trabalho estima o risco de infeção por SARS-CoV-2 em ambientes interiores onde a elevada densidade de ocupação resulta numa probabilidade acrescida de contágio, como escolas, escritórios, supermercados, restaurantes e ginásios.Material e Métodos: Foram testadas várias condições nos espaços interiores, tais como a utilização e eficácia de máscaras, a ventilação, a utilização de equipamentos que permitem uma assepsia do ar recorrendo a filtros HEPA, a densidade de ocupação e o tempo de permanência nos espaços, tendo sido utilizado um modelo baseado na dispersão de partículas de aerossóis em espaços fechados e na acumulação e inalação destas partículas ao longo do tempo.Resultados: Os resultados mostraram que a substituição de máscaras sociais por máscaras com classificação FFP2 diminuiu o risco de infeção em 90% nas escolas. Em escolas com ventilação natural, a abertura das janelas na sua totalidade reduziu o risco de infeção em 64% comparativamente com o cenário de janelas fechadas. Nos espaços onde a ventilação mecânica é normalmente utilizada, a probabilidade de infeção reduziu significativamente quando os caudais de ar novo regulamentares foram duplicados (redução de 32% nos escritórios, 42% nos restaurantes, 24% nos supermercados e 46% nos ginásios). A filtragem de ar com filtros HEPA permitiu a redução da probabilidade de infeção em 72% nas escolas, escritórios e restaurantes e 61% nos ginásios. O tempo de permanência nos espaços foi também um fator relevante na variação da probabilidade de infeção, principalmente nas escolas onde se verificou que aulas mais curtas e com um maior número de intervalos reduzem o risco de infeção.Discussão: Os resultados evidenciam a importância de uma adequada ventilação em ambientes fechados, principalmente em locais onde a densidade de ocupação e os tempos de permanência são mais longos, sendo essencial a introdução de ar exterior no interior dos espaços, seja através de meios naturais ou mecânicos. É expectável que os valores de risco de infeção apresentados ao longo do trabalho estejam subvalorizados pelo facto do modelo utilizado apenas considerar a transmissão por partículas inferiores a 10 µm e por, ao assumir o distanciamento social, não incluir a transmissão de curto alcance. A vacinação não foi considerada no modelo pelo facto de ainda não estar disponível quando o trabalho foi realizado.Conclusão: Este estudo vem contribuir para a identificação de medidas que permitem um menor risco de transmissão viral, e consequentemente, uma maior segurança no interior dos espaços fechados.

OmniSARS2: A Highly Sensitive and Specific RT-qPCR-Based COVID-19 Diagnostic Method Designed to Withstand SARS-CoV-2 Lineage Evolution.

Extensive transmission of SARS-CoV-2 during the COVID-19 pandemic allowed the generation of thousands of mutations within its genome. While several of these become rare, others largely increase in prevalence, potentially jeopardizing the sensitivity of PCR-based diagnostics. Taking advantage of SARS-CoV-2 genomic knowledge, we designed a one-step probe-based multiplex RT-qPCR (OmniSARS2) to simultaneously detect short fragments of the SARS-CoV-2 genome in ORF1ab, E gene and S gene. Comparative genomics of the most common SARS-CoV-2 lineages, other human betacoronavirus and alphacoronavirus, was the basis for this design, targeting both highly conserved regions across SARS-CoV-2 lineages and variable or absent in other Coronaviridae viruses. The highest analytical sensitivity of this method for SARS-CoV-2 detection was 94.2 copies/mL at 95% detection probability (~1 copy per total reaction volume) for the S gene assay, matching the most sensitive available methods. In vitro specificity tests, performed using reference strains, showed no cross-reactivity with other human coronavirus or common pathogens. The method was compared with commercially available methods and detected the virus in clinical samples encompassing different SARS-CoV-2 lineages, including B.1, B.1.1, B.1.177 or B.1.1.7 and rarer lineages. OmniSARS2 revealed a sensitive and specific viral detection method that is less likely to be affected by lineage evolution oligonucleotide-sample mismatch, of relevance to ensure the accuracy of COVID-19 molecular diagnostic methods.

REFLEXÕES ACERCA DO USO DA TELEMEDICINA NO BRASIL: OPORTUNIDADE OU AMEAÇA?

Os avanços tecnológicos trouxeram uma nova realidade de trabalho e assistěncia oferecida pelos profissionais de saúde. A utilizaçao das tecnologías para prover assistěncia, promoçao e educaçao em saúde é também denominada como saúde digital, e engloba, dentre outros, a telemedicina, inerente especificamente a prática da medicina a distancia. A telemedicina vem sido desenvolvida há muitas décadas e com diversas experiěncias nas mais variadas culturas e realidades socioeconómicas, atuando como ferramenta de teleassistěncia, teleconsulta, tele expertise, monitoramento remoto, pesquisas multicěntricas e atividades educacionais. Este artigo objetiva apresentar uma revisao crítica acerca do uso da telemedicina medicina no Brasil. O ponto alto das discussÐes acerca do tema refere-se, principalmente, a regulamentaçao da prática de teleconsultas, atividade utilizada em vários países e liberada no Brasil durante a pandemia de COVID-19. A literatura apresenta experiěncias e oportunidades do uso da telemedicina, tais quais: aumento do acesso a serviços de saúde, reduçao de deslocamentos de pacientes, reduçao de custos e aproximaçao de especialistas a populaçao de regiÐes remotas. Porém, uma recente tentativa de regulamentaçao do Conselho Federal de Medicina levantou uma série de discussÐes entre especialistas e assoc

Meckel's diverticulitis in a COVID-19 adult.

Meckel's diverticulitis is an unusual cause of acute abdomen condition in adults requiring prompt surgical treatment. We report a case of a 53-year-old male with coronavirus disease 19 (COVID-19), admitted to the emergency department with an acute abdominal pain. A computed tomography scan with intravenous contrast performed on the patient confirmed an inflamed short segment of the small bowel and the presence of a localized free peritoneal fluid. The definitive diagnosis was made intraoperatively, by means of an emergent ileal resection with primary anastomosis, which confirmed Meckel's diverticulitis. Postoperative evolution was ordinary. The association of COVID-19 with the acute abdomen is found to be weak, therefore surgical consultation is advised to minimize delayed treatment.

The Paradigm Shift of Ophthalmology in the COVID-19 Era.

OBJECTIVE: To describe how a fixed regimen of intravitreal injections (IVI) was helpful to continue activity during the COVID-19 outbreak and lockdown and to address basic conditions to resume activity. METHODS: A fixed regimen of IVI was conceived to significantly reduce the number of visits while keeping a number of injections related to the best outcomes. We retrospectively collected data of surgeries performed in 2019 and in the first seven months of 2020 and from OCTs in the first semester of 2020. RESULTS: IVI per month, from January to July 2020, were 304, 291, 256, 204, 276, 297 and 322, respectively. Phacoemulsification surgeries in the same period were 397, 408, 171, 0, 304, 391 and 389. Posterior vitrectomies were 23, 21, 17, 10, 21, 28 and 25. Laser sessions were 44, 26, 33, 17, 23 and 33, respectively. OCTs dropped from a mean of 25.7 per day in the first half of March 2020 to 5.8 per day in the second half of March. A mean of 6.5 OCTs per day was made in April, rising to 19.1 in May and 39.5 in June. CONCLUSION: It was possible to keep the ophthalmological activity during the pandemic outbreak due to the existence of a pre-scheduled fixed regimen for IVI and to the availability of personal protective equipment. The air-borne nature of the peril we are facing addresses the need to evaluate the physical conditions of health facilities, including ventilation, size of waiting and consult rooms and the need to avoid elevators.