A specific combination of laboratory data is associated with overweight lungs in patients with COVID-19 pneumonia at hospital admission: secondary cross-sectional analysis of a randomized clinical trial.

Background: Lung weight may be measured with quantitative chest computed tomography (CT) in patients with COVID-19 to characterize the severity of pulmonary edema and assess prognosis. However, this quantitative analysis is often not accessible, which led to the hypothesis that specific laboratory data may help identify overweight lungs. Methods: This cross-sectional study was a secondary analysis of data from SARITA2, a randomized clinical trial comparing nitazoxanide and placebo in patients with COVID-19 pneumonia. Adult patients (≥18 years) requiring supplemental oxygen due to COVID-19 pneumonia were enrolled between April 20 and October 15, 2020, in 19 hospitals in Brazil. The weight of the lungs as well as laboratory data [hemoglobin, leukocytes, neutrophils, lymphocytes, C-reactive protein, D-dimer, lactate dehydrogenase (LDH), and ferritin] and 47 additional specific blood biomarkers were assessed. Results: Ninety-three patients were included in the study: 46 patients presented with underweight lungs (defined by ≤0% of excess lung weight) and 47 patients presented with overweight lungs (>0% of excess lung weight). Leukocytes, neutrophils, D-dimer, and LDH were higher in patients with overweight lungs. Among the 47 blood biomarkers investigated, interferon alpha 2 protein was higher and leukocyte inhibitory factor was lower in patients with overweight lungs. According to CombiROC analysis, the combinations of D-dimer/LDH/leukocytes, D-dimer/LDH/neutrophils, and D-dimer/LDH/leukocytes/neutrophils achieved the highest area under the curve with the best accuracy to detect overweight lungs. Conclusion: The combinations of these specific laboratory data: D-dimer/LDH/leukocytes or D-dimer/LDH/neutrophils or D-dimer/LDH/leukocytes/neutrophils were the best predictors of overweight lungs in patients with COVID-19 pneumonia at hospital admission. Clinical trial registration: Brazilian Registry of Clinical Trials (REBEC) number RBR-88bs9x and ClinicalTrials.gov number NCT04561219.

COVID 19 and one health: potential role of human and animals in SARS-COV-2 life cycle

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease (COVID-19) in humans has zoonotic tendencies, which can potentially provoke cross-species transmission, including human-to-animal and animal-to-human infection. Consequently, the objective was to analyze the scientific evidence regarding SARS-CoV-2 animal infections from potential human transmission. A systematic review was executed following the PRISMA guidelines, in the PubMed/Medline, Google Scholar and LILACS, using the descriptors combined in the following way: (("SARS-CoV-2” OR "COVID-19” OR "2019-nCoV”) AND (animals OR zoonosis)). The results contemplated the viral susceptibility of about thirty animal species when induced naturally and/or experimentally. The mink & hamster species demonstrated ostensible animal-human transmission. Overall, there have been more reports of human contamination by other species than human retransmission from the pathogen. The natural infection of the virus was discovered in domestic dogs & cats, wild cats, deer, minks, rabbits, and hamsters. Several animals, including the African green monkeys and rabbits, manifested high levels of viremia, respiratory secretions, and fecal excretions of infectious virus conducive to environmental/aerosol transmission. It is still inadequately documented the intrinsic role of such processes, such as, the animals' involvement in viral mutations, the emergence of new variants/lineages and the role of the animal host species. Accordingly, this research model type, natural and experimental analysis on varying animal species, corroborates the link between the two aforementioned forms of transmission. Epidemiological surveillance through extensive sequencing of the viral genomes of infected animals and humans can reveal the SARS-CoV-2 transmission routes and anticipate appropriate prophylactic strategies.

Acute Myocarditis Associated with Acute Myocardial Infarction.

Concomitant acute myocarditis and acute coronary thrombosis is a rare presentation of acute chest pain in the emergency department, although the association between acute infections with a variety of pathogens and an increased risk of myocardial infarction has been reported. A case of acute myocardial infarction associated with acute myocarditis caused by coronavirus 229E in a middle-aged man without risk factors for coronary artery disease is described here. Coronary CT angiography with late enhancement protocol revealed areas of myocarditis and infarction, and cardiac MRI and coronary angiography were then performed. © RSNA, 2021.

Risk of Global Developmental Delay in Infants Born from Mothers with COVID-19: A Cross-Sectional Study.

Purpose: To investigate the risk of global developmental delay in infants born from mothers with COVID-19. Patients and Methods: A cross-sectional study was conducted between March and November 2021, with 54 infants of both sexes aged between 1 and 12 months. Twenty-seven infants born from mothers diagnosed with COVID-19 during pregnancy composed the COVID-19 group, whereas infants born from mothers not exposed to COVID-19 composed the control group. Medical records and child health booklets provided neonatal and prenatal data. The Survey of Wellbeing of Young Children screened the risk of global developmental delay during a phone interview or home visit. Chi-squared, Mann-Whitney test, and binary logistic regression were applied. Results: The risk of motor developmental delay was identified in 15 infants (12 in the COVID-19 group), while 36 were at risk of behavioral alteration (22 in the COVID-19 group). The COVID-19 group presented a 6.3-fold risk of motor developmental delay. Motor developmental delay was also significantly associated with socioemotional alterations (odds ratio = 6.4, p = 0.01). Regarding families of infants in the COVID-19 group, 63% of the mothers presented risk of depression, 51.9% risk of substance abuse, 40.7% risk of food insecurity, and 7.4% risk of domestic violence. The inflexibility subscale of the survey was a statistically relevant variable for the socioemotional domain. Conclusion: Infants born from mothers with COVID-19 were at high risk of motor developmental delay and socioemotional alterations. Although, this study fills an important gap in the literature regarding the influence of maternal exposure to COVID-19 on infant development, new studies screening families with infants at risk of developmental delay may significantly impact maternal and child health-related indicators, such as physical health, emotional development and social behavior.

SARS-CoV-2 Spillback to Wild Coatis in Sylvatic-Urban Hotspot, Brazil.

We tested coatis (Nasua nasua) living in an urban park near a densely populated area of Brazil and found natural SARS-CoV-2 Zeta variant infections by using quantitative reverse transcription PCR, genomic sequencing, and serologic surveillance. We recommend a One Health strategy to improve surveillance of and response to COVID-19.

Depression Among Portuguese Pregnant Women During Covid-19 Lockdown: A Cross Sectional Study.

INTRODUCTION: Coronavirus disease 2019 was declared as a pandemic on March 2020. Research on its psychological effects is still lacking. Perinatal depression is a medical complication of pregnancy, especially in situations of stress. In this study, we aimed to investigate the presence of symptoms of depression in pregnant women during the lockdown period in Portugal. METHODS: This study consisted in a cross-sectional study among Portuguese pregnant women, who completed an online self-report questionnaire between 25th April and 30th April 2020. An anonymous online questionnaire was developed to assess depression and concerns related to COVID-19. This study was approved by the IRB of Hospital Dona Estefânia and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Eligibility criteria included pregnant women, ≥ 18 years and living in Portugal. The primary outcome was to evaluate the presence of depressive symptoms and its association to socio-demographic characteristics and to concerns related to COVID-19. RESULTS: A total of 1698 pregnant women were enrolled. The mean age was 31.9 years. 82.4% felt a negative impact of the pandemic in the surveillance of pregnancy and 43% felt insufficient support. 26.3% showed "possible depression" according to the EPDS. A regression analysis revealed the possibility of depression increased as the concerns about COVID increased and was lower for women with support. The possibility of depression was higher for women with psychiatric medical history. CONCLUSION: This study demonstrated a significant increase in clinically significant depressive symptoms in pregnant women during the lockdown. It also revealed some of the socio-demographic characteristics of women at risk for depression. If left untreated, depression tends to persist, affecting the woman and also the child. Our findings suggest that COVID-19 represents a serious challenge for this population and reinforce the urgent need for early detection and intervention on mental health issues during pregnancy, especially during the pandemic.

Rapid Evaluation of the Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus Tests.

The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n = 125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, 10 influenza A, 10 influenza B and 20 respiratory syncytial virus specimens. Results were compared to in-country standard-of-care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive percentage agreement (PPA) = 95.2%, negative percentage agreement (NPA) = 95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA = 100%, NPA = 98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus, respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard-of-care tests.

Leukocyte ratios are useful early predictors for adverse outcomes of COVID-19 infection.

Leukocyte biomarkers, including the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte-(MLR), platelet-to-lymphocyte (PLR) ratios and systemic immune-inflammation index (SII) have been associated with severity and mortality of patients with COVID-19. The purpose of this study was to evaluate the association of baseline leukocyte biomarkers calculated in the emergency department (ED) with the disease severity and mortality. This was a retrospective cohort study that evaluated 1,535 (mean age 57+18 years) patients with SARS-CoV-2 infection in the ED of a single reference center. Outcomes were severity, defined as intensive care unit (ICU) admission requirement, and in-hospital mortality. All leukocyte biomarkers were calculated in the ED before the hospital admission. Their ability to predict the severity and mortality was measured using receiver operating characteristic (ROC) curves. Severity and mortality were observed in 30.9% and 12.6% of the patients, respectively, and were significantly correlated with NLR, MLR, PLR and SII, but only NLR was independently associated with both outcomes on multivariate analysis. Analysis of ROC curves revealed that NLR (0.78 for severity and 0.80 for mortality) and SII (0.77 for severity and 0.75 for mortality) had the best ability to predict mortality, when compared to other ratios. The highest AUC was observed for NLR, employing cut-off points of 5.4 for severity and 5.5 for mortality. Leukocyte biomarkers, particularly NLR, are capable of predicting the severity and mortality of patients with SARS-CoV-2 infection and could be important adjunct tools to identify patients in the ED that are more prone to develop adverse outcomes.

Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children.

Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.

Impact of the COVID-19 pandemic on laboratory diagnosis of tuberculosis in southern Brazil / Impacto da pandemia de COVID-19 no diagnóstico laboratorial de tuberculose no sul do Brasil / Impacto de la pandemia COVID-19 en el diagnóstico de laboratorio de la tuberculosis en el sur de Brasil

Background and objectives: to understand the impact of the COVID-19 pandemic on tuberculosis (TB) diagnosis in different settings is essential to guide the establishment of appropriate TB control strategies. This study aimed to assess the influence of COVID-19 pandemic in laboratory diagnosis of TB in patients tested and diagnosed for TB. Methods: a data survey was carried out in the database of laboratories that perform TB diagnosis for the public health system in Rio Grande city (Rio Grande do Sul, Brazil). Results: there was a decrease of 1,368 to 735 (reduction of 46.3%) in the number of patients tested for TB in public diagnostic services in 2019 and 2020, respectively, and a decrease of 197 to 119 (reduction of 39.6%) in the number of new TB cases diagnosed. In contrast, the positivity rate was 14.4% in 2019 and 16.2% in 2020. Moreover, it was observed that the laboratory that performs the diagnostic service for Primary Health Care was the most affected, when compared to Tertiary Health Care. Conclusion: as a consequence of measures to control the spread of SARS-CoV-2, there was a reduction in TB testing and in the detection of new cases, especially in Primary Health Care, where patients with less need for hospitalization are received.(AU)

Justificativa e objetivos: compreender o impacto da pandemia COVID-19 no diagnóstico da tuberculose (TB) em diferentes locais é essencial para orientar o estabelecimento de estratégias adequadas de controle da TB. O objetivo deste estudo foi avaliar a influência da pandemia de COVID-19 no diagnóstico laboratorial de TB, em pacientes testados e diagnosticados com TB. Métodos: foi realizado um levantamento de dados no banco de dados de laboratórios que realizam diagnóstico de TB para o sistema público de saúde na cidade de Rio Grande (Rio Grande do Sul, Brasil). Resultados: houve redução de 1.368 para 735 (redução de 46,3%) no número de pacientes testados para TB nos serviços públicos de diagnóstico em 2019 e 2020, respectivamente, e redução de 197 para 119 (redução de 39,6%) no número de novos casos de TB diagnosticados. Em contrapartida, a taxa de positividade foi de 14,4% em 2019 e 16,2% em 2020. Além disso, observou-se que o laboratório que realiza o serviço de diagnóstico para a Atenção Primária à Saúde foi o mais afetado, quando comparado com a Atenção Terciária à Saúde. Conclusão: como consequência das medidas de controle da disseminação do SARS-CoV-2, houve redução na testagem de TB e na detecção de novos casos, principalmente na atenção primária à saúde, onde são recebidos pacientes com menor necessidade de internação.(AU)

Justificación y objetivos: comprender el impacto de la pandemia Covid-19 en el diagnóstico de tuberculosis (TB) en diferentes lugares es fundamental para orientar el establecimiento de estrategias adecuadas de control de la TB. El objetivo de este estudio fue evaluar la influencia de la pandemia de COVID-19 en el diagnóstico de laboratorio de TB, en términos de pacientes examinados y diagnosticados de TB. Métodos: los datos fueron recolectados de la base de datos de los laboratorios que realizan el diagnóstico de TB para el sistema público de salud en la ciudad de Rio Grande (Rio Grande do Sul, Brasil). Resultados: hubo una reducción de 1.368 a 735 (reducción del 46,3%) en el número de pacientes sometidos a pruebas de TB en los servicios públicos de diagnóstico en 2019 y 2020, respectivamente, y una reducción de 197 a 119 (reducción del 39,6%) en el número de nuevos casos de TB diagnosticados. Por otro lado, la tasa de positividad fue de 14,4% en 2019 y 16,2% en 2020. Además, se observó que el laboratorio que realiza el servicio de diagnóstico para la Atención Primaria de Salud fue el más afectado, en comparación con la Atención Terciaria de Salud. Conclusiones: como consecuencia de las medidas para el control de la propagación del SARS-CoV-2, hubo una reducción en las pruebas de TB y en la detección de nuevos casos, especialmente en la Atención Primaria de Salud, donde se encuentran los pacientes con menor necesidad de hospitalización.(AU)

The Lockdown Impact on the Relations between Portuguese Parents and Their 1- to 3-Year-Old Children during the COVID-19 Pandemic.

Many countries have applied mandatory confinement measures in response to the COVID-19 pandemic, such as school and kindergarten closures, which confined families to their homes. The study concerns the impacts of the first COVID-19 lockdown on the relationships between Portuguese parents and their children, in a non-clinical population composed of fathers and mothers of children between the ages of 12 months and 3 years and 364 days. An online questionnaire (set by the research team) and the Parenting Daily Hassles Scale (PDHS) concerning the confinement period were applied between 17 June and 29 July 2020. To assess the impacts of the lockdown, outcomes regarding the impacts perceived by the parents, the potential regression in the development of children, and the willingness to promote changes in family routines in the future, were considered. Of the total sample (n = 1885), 95.4% of the parents (n = 1798) said that, after confinement, the relationship with their children had improved or remained similar to the pre-confinement period; 97.3% (n = 1835) noticed positive changes in the development of their children, and 63.7% (n = 1200) noted that the relationships with their children during the confinement period would lead to some changes in family routines in the future. Multivariate regression analyses showed that most of the sociodemographic variables chosen were not associated with the outcomes. However, significant levels of pressure over parenting and parental overload (reported by high scores in the PDHS intensity and frequency scales), challenging behaviors of the children, and the impacts they had on parental tasks had negative influences on the studied outcomes. On the contrary, the number of adults living with their children, the perceptions regarding the development of their children, and sharing new experiences with them were significant factors for positively-perceived impacts on the relationships between them or in the desire to bring about changes in family routines in the future. The impacts of the lockdown on the relationships between parents and children aged between 1 and 3 years old were more dependent on relational aspects and on the parents' sense of competence in exercising parental functions. We conclude that, despite the increased demands imposed by the lockdown, nearly all of the parents evaluated the quality of the relationship with their children as positive after this period.

UV-C irradiation-based inactivation of SARS-CoV-2 in contaminated porous and non-porous surfaces.

The SARS-CoV-2 pandemic emphasized effective cleaning and disinfection of common spaces as an essential tool to mitigate viral transmission. To address this problem, decontamination technologies based on UV-C light are being used. Our aim was to generate coherent and translational datasets of effective UV-C-based SARS-CoV-2 inactivation protocols for the application on surfaces with different compositions. Virus infectivity after UV-C exposure of several porous (bed linen, various types of upholstery, synthetic leather, clothing) and non-porous (types of plastic, stainless steel, glass, ceramics, wood, vinyl) materials was assessed through plaque assay using a SARS-CoV-2 clinical isolate. Studies were conducted under controlled environmental conditions with a 254-nm UV-C lamp and irradiance values quantified using a 254 nm-calibrated sensor. From each material type (porous/non-porous), a product was selected as a reference to assess the decrease of infectious virus particles as a function of UV-C dose, before testing the remaining surfaces with selected critical doses. Our data show that UV-C irradiation is effectively inactivating SARS-CoV-2 on both material types. However, an efficient reduction in the number of infectious viral particles was achieved much faster and at lower doses on non-porous surfaces. The treatment effectiveness on porous surfaces was demonstrated to be highly variable and composition-dependent. Our findings will support the optimization of UV-C-based technologies, enabling the adoption of effective customizable protocols that will help to ensure higher antiviral efficiencies.

NKG2A Expression among CD8 Cells Is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the BRACE CORONA Randomized Trial.

Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.

General methodological aspects in the Brazilian National Survey on Child Nutrition (ENANI-2019): a population-based household survey.

This article aims to present general methodological aspects of the Brazilian National Survey on Child Nutrition (ENANI-2019), from the conception of the study design to details of the data collection. This is a household-based population survey with a sample calculated at 15,000 households to identify children under five years of age, conducted in 123 municipalities in Brazil's 26 states and the Federal District. ENANI-2019 includes data on breastfeeding and dietary intake; anthropometric nutritional status of all children and their biological mothers; and nutritional status concerning the following micronutrients: iron (hemoglobin and ferritin), zinc, selenium, and vitamins A, B1, B6, B12, D, E, and folic acid of children from 6 to 59 months of age. A total of 193,212 households were visited, of which 19,951 were eligible, and 12,524 were included in the study. A total of 14,558 children were studied, of whom 13,990 (96.1%) and 13,921 (95.6%) had their body mass and length/stature measured, respectively, and 14,541 (99.9%) underwent 24-hour dietary recalls (24HR). Of the 12,598 children eligible for blood sample collection, 8,739 (69.3%) had at least one laboratory parameter measured. Data were collected from February 2019 to March 2020, when the survey was interrupted due to the COVID-19 pandemic. The evidence produced by the ENANI-2019 survey can back the formulation, follow-up, and/or reorientation of food and nutrition policies such as the promotion of breastfeeding and healthy eating and the prevention and control of different forms of malnutrition.

Rationale and limitations of the SpO2/FiO2 as a possible substitute for PaO2/FiO2 in different preclinical and clinical scenarios. / Justificativa e limitações da SpO2/FiO2 como possível substituta da PaO2/FiO2 em diferentes cenários pré-clínicos e clínicos.

Although the PaO 2/FiO 2 derived from arterial blood gas analysis remains the gold standard for the diagnosis of acute respiratory failure, the SpO2/FiO2 has been investigated as a potential substitute. The current narrative review presents the state of the preclinical and clinical literature on the SpO2/FiO2 as a possible substitute for PaO2/FiO2 and for use as a diagnostic and prognostic marker; provides an overview of pulse oximetry and its limitations, and assesses the utility of SpO2/ FiO2 as a surrogate for PaO2/FiO2 in COVID-19 patients. Overall, 49 studies comparing SpO2/FiO2 and PaO2/FiO2 were found according to a minimal search strategy. Most were conducted on neonates, some were conducted on adults with acute respiratory distress syndrome, and a few were conducted in other clinical scenarios (including a very few on COVID-19 patients). There is some evidence that the SpO2/ FiO2 criteria can be a surrogate for PaO2/FiO2 in different clinical scenarios. This is reinforced by the fact that unnecessary invasive procedures should be avoided in patients with acute respiratory failure. It is undeniable that pulse oximeters are becoming increasingly widespread and can provide costless monitoring. Hence, replacing PaO2/FiO2 with SpO2/FiO2may allow resourcelimited facilities to objectively diagnose acute respiratory failure.

Embora a PaO2/FiO2 derivada da gasometria arterial continue sendo o padrão-ouro do diagnóstico de insuficiência respiratória aguda, a SpO2/FiO2 tem sido investigada como potencial substituta. Esta revisão narrativa apresenta o estado da literatura pré-clínica e clínica sobre a SpO2/FiO2 como possível substituta da PaO2/FiO2 e para uso como marcador diagnóstico e prognóstico; ainda, é fornecida uma visão geral da oximetria de pulso e suas limitações, além da avaliação da utilidade da SpO2/ FiO2 como substituta da PaO2/FiO2 em pacientes com COVID-19. Ao todo, foram encontrados 49 estudos comparando SpO2/FiO2 e PaO2/ FiO2 com base em uma estratégia de pesquisa mínima. A maioria dos estudos foi realizada em recémnascidos, alguns foram realizados em adultos com síndrome do desconforto respiratório agudo, e outros foram realizados em outros cenários clínicos (incluindo poucos em pacientes com COVID-19). Há certa evidência de que os critérios de SpO2/FiO2 podem substituir a PaO2/FiO2 em diferentes cenários clínicos. Isso é reforçado pelo fato de que devem ser evitados procedimentos invasivos desnecessários em pacientes com insuficiência respiratória aguda. É inegável que os oxímetros de pulso estão cada vez mais difundidos e podem proporcionar um monitoramento sem custos. Portanto, substituir a PaO2/FiO2 pela SpO2/FiO2 pode permitir que instalações com recursos limitados diagnostiquem a insuficiência respiratória aguda de maneira objetiva.

Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.

Validity and reliability of a new incremental step test for people with chronic obstructive pulmonary disease.

BACKGROUND: Incremental step tests (IST) can be used to assess exercise capacity in people with chronic obstructive pulmonary disease (COPD). The development of a new step test based on the characteristics of the incremental shuttle walk test (ISWT) is an important study to explore. We aimed to develop a new IST based on the ISWT in people with COPD, and assess its validity (construct validity) and reliability, according to Consensus-based Standards for the selection of health status Measurement Instruments (COSMIN) recommendations. METHODS: A cross-sectional study was conducted in participants recruited from hospitals/clinics. During the recruitment, the participants who presented a 6-minute walk test (6MWT) report in the previous month were also identified and the respective data was collected. Subsequently, participants attended two sessions at their homes. IST was conducted on the first visit, along with the 1 min sit-to-stand (1MSTS) test. IST was repeated on a second visit, performed 5-7 days after the first one. Spearman's correlations were used for construct validity, by comparing the IST with the 6MWT and the 1MSTS. Intraclass correlation coefficient (ICC2,1), SE of measurement (SEM) and minimal detectable change at 95% CI (MDC95) were used for reliability. The learning effect was explored with the Wilcoxon signed-rank test. RESULTS: 50 participants (70.8±7.5 years) were enrolled. IST was significant and moderate correlated with the 6MWT (ρ=0.50, p=0.020), and with the 1MSTS (ρ=0.46, p=0.001). IST presented an ICC2,1=0.96, SEM=10.1 (16.6%) and MDC95=27.9 (45.8%) for the number of steps. There was a statistically significant difference between the two attempts of the IST (p=0.030). CONCLUSION: Despite the significant and moderate correlations with the 6MWT and 1MSTS, the inability to full compliance with the COSMIN recommendations does not yet allow the IST to be considered valid in people with COPD. On the other hand, the IST is a reliable test based on its high ICC, but a learning effect and an 'indeterminate' measurement error were shown. TRIAL REGISTRATION NUMBER: NCT04715659.

Can Epigenetics Help Solve the Puzzle Between Concomitant Cardiovascular Injury and Severity of Coronavirus Disease 2019?

ABSTRACT: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has significant implications in patients with concomitant cardiovascular disease (CVD) because they are the population at the greatest risk of death. The treatment of such patients and complications may represent a new challenge for the fields of cardiology and pharmacology. Thus, understanding the involvement of this viral infection in CVD might help to reduce the aggressiveness of SARS-CoV-2 in causing multiorgan infection and damage. SARS-CoV-2 disturbs the host epigenome and several epigenetic processes involved in the pathophysiology of COVID-19 that can directly affect the function and structure of the cardiovascular system (CVS). Hence, it would be relevant to identify epigenetic alterations that directly impact CVS physiology after SARS-CoV-2 infection. This could contribute to the view of this virus-induced CVS injury and direct forthcoming tackles for COVID-19 treatment to reduce mortality in patients with CVD. Targeting epigenetic marks could offer strong evidence for the development of novel antiviral therapies, especially in the context of COVID-19-related CVS damage. In this review, we address some of the main signaling pathways that are currently known as being involved in COVID-19 pathophysiology and the importance of this glint on epigenetics and some of its modifiers (epidrugs) to control the unregulated epitope activity in the context of SARS-CoV-2 infection, COVID-19, and underlying CVD.

Discontinuing vs continuing ACEIs and ARBs in hospitalized patients with COVID-19 according to disease severity: Insights from the BRACE CORONA trial.

BACKGROUND: We explored the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with COVID-19 according to baseline disease severity. METHODS: We randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity. RESULTS: At presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 [SD 6.3] days) and continuation (mean 23.8 [SD 6.5] days), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 [SD 9.5] days) than continuation (mean 21.6 [SD 7.6] days), with a mean ratio of 0.90 (95% CI 0.81-1.00; P-interaction = .01). The impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity. CONCLUSIONS: Unlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04364893).

Understanding the pathophysiology of typical acute respiratory distress syndrome and severe COVID-19.

INTRODUCTION: Typical acute respiratory distress syndrome (ARDS) and severe coronavirus-19 (COVID-19) pneumonia share complex pathophysiology, a high mortality rate, and an unmet need for efficient therapeutics. AREAS COVERED: This review discusses the current advances in understanding the pathophysiologic mechanisms underlying typical ARDS and severe COVID-19 pneumonia, highlighting specific aspects of COVID-19-related acute hypoxemic respiratory failure that require attention. Two models have been proposed to describe the mechanisms of respiratory failure associated with typical ARDS and severe COVID-19 pneumonia. EXPERT OPINION: ARDS is defined as a syndrome rather than a distinct pathologic entity. There is great heterogeneity regarding the pathophysiologic, clinical, radiologic, and biological phenotypes in patients with ARDS, challenging clinicians, and scientists to discover new therapies. COVID-19 has been described as a cause of pulmonary ARDS and has reopened many questions regarding the pathophysiology of ARDS itself. COVID-19 lung injury involves direct viral epithelial cell damage and thrombotic and inflammatory reactions. There are some differences between ARDS and COVID-19 lung injury in aspects of aeration distribution, perfusion, and pulmonary vascular responses.