Evolution of fibrotic interstitial lung diseases (ILD) after COVID-19

Introduction: Data about the impact of COVID-19 on patients with fibrotic ILD are limited. These patients have impaired lung function and increased risk of acute exacerbation driven by viral infection, so COVID-19 is of particular concern. Aim(s): To evaluate the impact of SARS-CoV-2 infection on patients with previous fibrotic ILD. Method(s): Single-center retrospective study including adult patients with previous fibrotic ILD and SARS-CoV-2 infection. Clinical, imaging, and respiratory functional data, pre and post infection, were revised. Result(s): A total of 49 patients (median age 68.4+/-11.1 years, 61.2% male) were analysed and major comorbidities included dyslipidaemia (69.4%), hypertension (53.1%) and obesity (29.9%). Hypersensitivity pneumonitis was the most frequent diagnosis (22.4%) followed by CTD-ILD (20.4%). Non-corticosteroid immunosuppression was present in 38.8% of the cases. Regarding COVID-19 severity, most cases were mild (55.1%) and 34.7% were severe disease requiring hospitalization. Fifteen patients died and 14 patients experienced progression of fibrosis, which was associated with a significant clinical (mean mMRC 0.86+/-0.53 vs 1.57+/-1.09, p=0.015) and DLCO decline (5.12+/-2.57 vs 4.54+/-2.96, p=0.002). Independent predictor of fibrotic worsening was the absence of non-corticosteroid immunosuppression (OR 0.072, p=0.019). Mortality correlated with OSA (p=0.011), heart failure (p=0.032), previous hypoxemic respiratory failure (p=0.013), severe COVID-19 disease (p<0.001) and hospitalization (p=0.004). Conclusion(s): Non-corticosteroid immunosuppression may have a protective role in fibrotic ILD patients. Mortality associated with COVID-19 severity, OSA, heart failure and previous hypoxemic respiratory failure.

COVID-19 in interstitial lung diseases: are fibrotic ILDs associated with worse outcomes?

Introduction: Few studies have evaluated the impact of COVID-19 on interstitial lung diseases (ILDs). Our aim was to compare outcomes in patients with fibrotic-ILDs (F-ILDs) and non-fibrotic-ILDs (NF-ILDs) after COVID-19. Method(s): We reviewed patients with ILD followed in a Portuguese university hospital. Patients' features and COVID- 19 outcomes were compared between F-ILDs and NF-ILDs groups. We used Kaplan-Meyer analysis to estimate overall survival (OS) and cox-proportional-hazards regression models to identify factors associated with OS. Result(s): A total of 103 patients (49.5% were male;mean age of 61.5+/-14.5 years) were included. The most prevalent ILDs were sarcoidosis (26.2%), HP (14.6%), CTD-ILD (14.6%), OP (8.7%), IPF (7.8%) and unclassifiable idiopathic interstitial pneumonia (7.8%). 47.6% of patients had F-ILD, and they had a higher prevalence of dyslipidemia (p=0.006) and immunosuppressive therapy (p<.001). Regarding the severity of COVID-19, 64.7% had mild, 11.7% moderate and 24.3% severe disease. There was a higher proportion of severe disease among F-ILDs patients (34.7% vs 14.8%, p=0.019). Post-COVID-19 mortality (median follow-up of 44 weeks) was significantly higher in FILD than NF-ILD cases (30.6% vs 5.6%, p=0.001). The median OS was significantly lower for patients who had severe disease (18.0 vs 45.5 weeks;p<.001) and F-ILD (41 vs 45 weeks;p=0.001). According to multivariate analysis, F-ILD (HR:4.00, p=0.042) and severe disease (HR:6.98, p=0.008) were the factors associated with worse OS. Concluding: In our analysis, COVID-19 was associated with worse outcomes in patients with F-ILDs and severe COVID-19, regardless of cardiovascular risk factors.

What does caring HRD look like in practice? A case study of two social enterprises in Brazil

Impacts of COVID-19 pandemic, combined with an array of other severe threats to societal well-being (e.g. inequality, systemic racism, and environmental degradation), have shed light on the importance of ethics of care as a guiding normative for HRD. However, the current understanding of care as HRD practice is limited and primarily studied in the context of leaders' behaviours towards employees. This study addresses this shortcoming by conducting a case study of social enterprises located in impoverished communities surrounding the UNESCO World Heritage Site Serra da Capivara National Park, Brazil, to examine what caring HRD looks like and how it can be operationalised in organisations. We conducted a qualitative study based on interviews and documentation analysis to map the flow of care practices implemented by these social enterprises. Our findings suggest that caring HRD entails a reciprocal and systemic approach highly relevant to organisations operating in collaborative and complex social contexts. We observed that moral values are critical requirements for a caring approach and must be embedded in the organisation's mission, culture, and processes. Our work expands the range of care interventions proposed in HRD literature by offering strategies that target the whole organisational system, including the surrounding environment and community.

Impact of a home-based cardiac rehabilitation program in heart failure during the COVID-19 pandemic

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This work was financially supported by the project POCI-01-0145-FEDER-030011, funded by FEDER, through COMPETE2020-POCI, and by national funds, through FCT/MCTES (PTDC/MEC-CAR/30011/2017). CIAFEL, UnIC and UMIB are supported by national funds through Fundação para a Ciência e Tecnologia, I.P. [(UIDB/00617/2020), (UIDB/00051/2020 and UIDP/00051/2020), and (UIDB/00215/2020 and UIDP/00215/2020), respectively]. CS received an individual grant from CAPES [BEX 0554/14-6]. Introduction Cardiac rehabilitation (CR) is an evidence-based recommended treatment of heart failure (HF) patients. During the COVID-19 pandemic, the shutdown of CR centers was necessary to limit the infection risk among high-risk patients. The integration of a home-based CR (HBCR) program in CR units can help to improve the delivery of care and improve cardiovascular outcomes of HF patients. Purpose To assess the effectiveness of an HBCR program in HF patients. Methods This is a sub­study of the EXercise InTervention in Heart Failure trial (EXIT-HF), which include forty-nine HF patients (preserved and reduced ejection fraction). The HBCR program consisted in 12-week combined exercise program (60%-80% of peak oxygen consumption (VO2 peak)), 2 training sessions per week, for a total of 24 sessions. Patients performed 4 supervised training sessions and the remaining sessions at home. All patients performed a cardiopulmonary exercise test (VO2 peak), the 6-minute-walking test (6MWT), collected blood analysis (plasma NT-proBNP), and answered the Minnesota Living with Heart Failure Questionnaire. Results Forty-two patients (86%) complete at least 80% of prescribed training sessions (age: 61.1±12;FEVE: 37.1±10.8). The HBCR program improve VO2 peak from 18.3 to 20.1ml/kg/min (+1.8 ml/kg/min;95%IC:1.4 to 2.4;p<0.001) and the walked distance at the 6MWT from 462 to 512 meters (+49 meters;95%IC: 38 to 60;p<0.001). In addition, overall quality of life was improved (-13 points;95%IC:-7.8 to -18.5;p<0.001), as well physical (-6.3 points;95%IC:-3.5 to -9;p<0.001) and emotional dimension of quality of life (-2.8points ;95%IC: -0.9 to -4.7;p=0.06). No significant change was found in NT-proBNP levels (820±1220 vs 674±903;p=0.285). Conclusions Our results showed that HBCR is feasible and can improve functional capacity and quality of life in HF patients.

Home-based cardiac rehabilitation can reduce anxiety and depression in heart failure patients

Introduction: The current COVID-19 pandemic has led to significant changes in physical and mental health and has become a major challenge for cardiac rehabilitation (CR) programs. CR is an essential component in the treatment of heart failure (HF), as it improves cardiorespiratory fitness and quality of life, as well as reducing hospitalization rates. COVID-19 pandemic increased social isolation, and the CR centers were closed. Center-based CR requires the patient to travel to the hospital, which increases the risk of SARS-CoV-2 infection in this high-risk population. In this context, home-based CR can be an excellent strategy to reduce the physical and mental consequences of the social isolation imposed by the COVID-19 pandemic. Objective: To test the effectiveness of a home-based CR program on cardiorespiratory fitness and anxiety and depression levels in individuals with HF during covid-19 pandemic. Methods: Forty-two individuals with HF (age: 61.3±12.0;LVEF: 37.5±11.2) were included in this study. The exercise training program consisted in 12 weeks of combined exercise training (2x/week;60min/day, 60-80% VO2peak), with 4 supervised exercise sessions in the hospital context and the remaining at home. Patients were monitored using a heart rate monitor and weekly phone calls. The following parameters were evaluated: cardiorespiratory fitness through the 6-minute walk test (6MWT) and anxiety and depression levels through the Hospital Anxiety and Depression Scale (HADS). Results: After the home-based CR program, there was a significant increase in the 6MWT of 49 meters (95%IC: 38 to 60;p<0.001) and a significant decrease in anxiety levels of -1.12 points (95%CI: - 2.163 to -0.075 p=0.036). No significant changes were found in depression levels (p=0.954). Furthermore, the improvements in cardiorespiratory fitness were significantly associated with the reduction in the levels of anxiety (r= -0.281;p=0.028) and depression (r=: -0.278;p=0.030). Conclusions: The home-based CR program was able to improve cardiorespiratory fitness and this improvement was associated with a decrease in anxiety and depression levels in individuals with HF. The results suggest that home-based CR can be an important strategy to minimize the physical and mental impact induced by social isolation imposed by COVID-19 pandemic in HF patients.

New In Silico Insights into the Application of (Hydroxy)Chloroquine with Macrolide Antibiotic Co-Crystals against the SARS-CoV-2 Virus

In this in silico study, different pharmaceutical co-crystals based on (hydroxy)chloroquine with macrolide antibiotics (azithromycin, clarithromycin, or erythromycin A) were analyzed for the first time. These findings present a new molecular perspective and therefore suggest that the combination of (hydroxy)chloroquine/azithromycin, in the stoichiometric ratio of 1:1, as model co-crystal systems has less toxicity and is the most effective for inhibiting the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention.

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.

Physical exercise and COVID-19 pandemic in PubMed: Two months of dynamics and one year of original scientific production.

Our aim was to conduct a narrative review about physical exercise and Corona Virus Disease 2019 (COVID-19). A literature search was completed crossing the keywords "COVID-19" and "physical exercise", for a narrative review, and physical activity (PA), physical exercise, physical training, sport, physical fitness, for a systematic review; search strategy (Randomized Controlled Trial, in the last 1 year, English). The first search date was closed on 04/26/2020 and 06/26/2020. This strategy was chosen to assess the dynamics of scientific information production for the pandemic. In two months, an increase of 76%, from 12 (19.4%) to 50 (80.64%) COVID-19 articles (n = 62, 100%) was found. The main types of articles published were editorial articles (16.13%, n = 10 of 62 articles) and commentary (9.68%, n = 6 of 62 articles). The most frequent country of origin of the scientific production was the United States (12.90%, n = 8 of 62 articles), the United Kingdom (12.90%, n = 8 of 62 articles), and Brazil (11.29%, n = 7 of 62 articles). However, in 2020, there were only 2 relevant randomized controlled trials on the COVID-19 topic in the context of physical exercise. Scientific information production shows the concern of the PA science community to bring a solution to the increase in physical inactivity generated by the COVID-19 pandemic. Our findings show the dynamics of scientific production on the COVID-19, in a situation so unique such as a pandemic, denotes that the practice of PA is essential to improve and/or maintain physical and mental health.

Determinants of COVID-19 Mortality in Patients With Cancer From a Community Oncology Practice in Brazil.

PURPOSE: The COVID-19 pandemic remains a public health emergency of global concern. Determinants of mortality in the general population are now clear, but specific data on patients with cancer remain limited, particularly in Latin America. MATERIALS AND METHODS: A longitudinal multicenter cohort study of patients with cancer and confirmed COVID-19 from Oncoclínicas community oncology practice in Brazil was conducted. The primary end point was all-cause mortality after isolation of the SARS-CoV-2 by Real-Time Polymerase Chain Reaction (RT-PCR) in patients initially diagnosed in an outpatient environment. We performed univariate and multivariable logistic regression analysis and recursive partitioning modeling to define the baseline clinical determinants of death in the overall population. RESULTS: From March 29 to July 4, 2020, 198 patients with COVID-19 were prospectively registered in the database, of which 167 (84%) had solid tumors and 31 (16%) had hematologic malignancies. Most patients were on active systemic therapy or radiotherapy (77%), largely for advanced or metastatic disease (64%). The overall mortality rate was 16.7% (95% CI, 11.9 to 22.7). In univariate models, factors associated with death after COVID-19 diagnosis were age ≥ 60 years, current or former smoking, coexisting comorbidities, respiratory tract cancer, and management in a noncurative setting (P < .05). In multivariable logistic regression and recursive partitioning modeling, only age, smoking history, and noncurative disease setting remained significant determinants of mortality, ranging from 1% in cancer survivors under surveillance or (neo)adjuvant therapy to 60% in elderly smokers with advanced or metastatic disease. CONCLUSION: Mortality after COVID-19 in patients with cancer is influenced by prognostic factors that also affect outcomes of the general population. Fragile patients and smokers are entitled to active preventive measures to reduce the risk of SARS-CoV-2 infection and close monitoring in the case of exposure or COVID-19-related symptoms.

Computational evidence for nitro derivatives of quinoline and quinoline N-oxide as low-cost alternative for the treatment of SARS-CoV-2 infection.

A new and more aggressive strain of coronavirus, known as SARS-CoV-2, which is highly contagious, has rapidly spread across the planet within a short period of time. Due to its high transmission rate and the significant time-space between infection and manifestation of symptoms, the WHO recently declared this a pandemic. Because of the exponentially growing number of new cases of both infections and deaths, development of new therapeutic options to help fight this pandemic is urgently needed. The target molecules of this study were the nitro derivatives of quinoline and quinoline N-oxide. Computational design at the DFT level, docking studies, and molecular dynamics methods as a well-reasoned strategy will aid in elucidating the fundamental physicochemical properties and molecular functions of a diversity of compounds, directly accelerating the process of discovering new drugs. In this study, we discovered isomers based on the nitro derivatives of quinoline and quinoline N-oxide, which are biologically active compounds and may be low-cost alternatives for the treatment of infections induced by SARS-CoV-2.

Differences among Severe Cases of Sars-CoV-2, Influenza, and Other Respiratory Viral Infections in Pediatric Patients: Symptoms, Outcomes and Preexisting Comorbidities

OBJECTIVES: Previous studies focusing on pediatric patients hospitalized with severe coronavirus disease 2019 (COVID-19) have been limited to small case series. We aimed to evaluate the characteristics of a large population of pediatric patients with severe COVID-19 and compare them with patients with severe cases of influenza and other respiratory viruses (ORV). METHODS: We performed a cross-sectional study of Brazilian data from the National Epidemiological Surveillance Information System, gathered from January 1st to July 14th, 2020. The sample included 4,784 patients (2,570 with confirmed COVID-19, 659 with influenza, 1,555 with ORV). Outcome measures included clinical features, preexisting comorbidities, pediatric intensive care unit admissions, need for ventilatory support, and death. RESULTS: Compared with the influenza and ORV groups, the COVID-19 group had a higher proportion of newborns and adolescents, as well as lower frequencies of fever, cough, dyspnea, respiratory distress, and desaturation. Although use of invasive ventilatory support was similar among groups, death rate was highest for COVID-19 (15.2% vs. 4.5% vs. 3.2%, p&lt;0.001), with death risk more than three times the other groups (adjusted OR=3.7 [95% CI 2.5-5.6]). The presence of two or more comorbidities further increased this risk (OR=4.8 [95% CI 3.5-6.6]). Preexisting comorbidities were reported in 986 patients with severe COVID-19 (38%). Mortality rate among COVID-19 patients was significantly higher for almost all comorbidities reported. CONCLUSION: Severe COVID-19 had a higher mortality rate than other viral respiratory illnesses, despite the lower frequency of fever, cough, dyspnea, respiratory distress, and desaturation. Death risk was strongly associated with preexisting comorbidities.

Differences among Severe Cases of Sars-CoV-2, Influenza, and Other Respiratory Viral Infections in Pediatric Patients: Symptoms, Outcomes and Preexisting Comorbidities

OBJECTIVES: Previous studies focusing on pediatric patients hospitalized with severe coronavirus disease 2019 (COVID-19) have been limited to small case series. We aimed to evaluate the characteristics of a large population of pediatric patients with severe COVID-19 and compare them with patients with severe cases of influenza and other respiratory viruses (ORV). METHODS: We performed a cross-sectional study of Brazilian data from the National Epidemiological Surveillance Information System, gathered from January 1st to July 14th, 2020. The sample included 4,784 patients (2,570 with confirmed COVID-19, 659 with influenza, 1,555 with ORV). Outcome measures included clinical features, preexisting comorbidities, pediatric intensive care unit admissions, need for ventilatory support, and death. RESULTS: Compared with the influenza and ORV groups, the COVID-19 group had a higher proportion of newborns and adolescents, as well as lower frequencies of fever, cough, dyspnea, respiratory distress, and desaturation. Although use of invasive ventilatory support was similar among groups, death rate was highest for COVID-19 (15.2% vs. 4.5% vs. 3.2%, p&lt;0.001), with death risk more than three times the other groups (adjusted OR=3.7 [95% CI 2.5-5.6]). The presence of two or more comorbidities further increased this risk (OR=4.8 [95% CI 3.5-6.6]). Preexisting comorbidities were reported in 986 patients with severe COVID-19 (38%). Mortality rate among COVID-19 patients was significantly higher for almost all comorbidities reported. CONCLUSION: Severe COVID-19 had a higher mortality rate than other viral respiratory illnesses, despite the lower frequency of fever, cough, dyspnea, respiratory distress, and desaturation. Death risk was strongly associated with preexisting comorbidities.

The economic impacts of COVID-19 in Brazil based on an interregional CGE approach

This study projects the economic impacts of COVID-19 outbreak on the Brazilian economy using a dynamic interregional computable general equilibrium model. We considered two scenarios. The first scenario has two channels of transmission over the economic system: a negative shock of labor supply due to the rates of morbidity and mortality caused by the pandemic, and a temporary shutdown of nonessential economic activities. The second scenario adds to the first the effects of the government fiscal package adopted to counteract the effects of COVID-19 on the economy. Furthermore, in both scenarios, a sensitive analysis related to the temporality of the shutdown is considered by assuming 3 and 6 months of shutdown. The results indicate a reduction of 3.78% in the national GDP growth rate in Scenario 1 and a reduction of 0.48% in Scenario 2, in 2020, with 3 months of shutdown. With 6 months, the reduction would be greater, 10.90% and 7.64% in Scenarios 1 and 2, respectively. Thus, the government fiscal stimulus considered in this study partially mitigates the reduction in GDP projected under the COVID-19 outbreak. The study also presents sectoral projections at the national and state levels. The estimates indicate reductions in the GDP of most of Brazilian states in both scenarios.

Theoretical Insights into the Effect of Halogenated Substituent on the Electronic Structure and Spectroscopic Properties of the Favipiravir Tautomeric Forms and Its Implications on the Treatment of COVID-19 (preprint)

In this study, we systematically investigated the electronic structure, spectroscopic (nuclear magnetic resonance, infrared, Raman, electron ionization mass spectrometry, UV-Vis, circular dichroism, and emission) properties, and tautomerism of halogenated favipiravir compounds (fluorine, chlorine, and bromine) from a computational perspective. Additionally, the effects of hydration on the proton transfer mechanism of the tautomeric forms of the halogenated favipiravir compounds are discussed. Our results suggest that spectroscopic properties allow for the elucidation of such tautomeric forms. As is well-known, the favipiravir compound has excellent antiviral properties and hence was recently tested for the treatment of new coronavirus (SARS-CoV-2). Through in silico modeling, in the current study, we evaluate the role of such tautomeric forms in order to consider the effect of drug-metabolism into the inhibition process of the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 virus. These findings clearly indicated that all title compounds are better as RNA-inhibiting.

New in silico insights into the application of the (hydroxy)chloroquine with macrolide antibiotics co-crystals against the SARS-CoV-2 virus (preprint)

In this in silico study, the different pharmaceutical co-crystals based on the (hydroxy)chloroquine with the macrolide antibiotics (azithromycin, clarithromycin, or erythromycin A) was analyzed for the first time. These findings present a new molecular perspective and, therefore, suggest that the combination of (hydroxy)chloroquine/azithromycin, in the stoichiometric ratio of 1:1, as model co-crystals systems have less toxicity as well as is the most effective for inhibiting the new coronavirus SARS-CoV-2.

Cardiovascular Imaging and Interventional Procedures in Patients with Novel Coronavirus Infection. / Imagem Cardiovascular e Procedimentos Intervencionistas em Pacientes com Infecção pelo Novo Coronavírus.

The coronavirus disease 2019 (COVID-19) pandemic is a huge challenge to the health system because of the exponential increase in the number of individuals affected. The rational use of resources and correct and judicious indication for imaging exams and interventional procedures are necessary, prioritizing patient, healthcare personnel, and environmental safety. This review was aimed at guiding health professionals in safely and effectively performing imaging exams and interventional procedures.

Construction and validation of checklist for disinfecting ambulances to transport Covid-19 patients

OBJECTIVE: To build and validate a checklist for disinfecting ambulances transporting patients with Covid-19. METHOD: Methodological study composed by the construction of a checklist and validation by 42 professionals, of which 35 professionals had expertise in patient transport/transfer and seven in hospital infection control. The item with a minimum agreement of 80% was considered valid, based on the Content Validation Index and binomial test. RESULTS: The checklist had the steps performed for terminal disinfection of ambulances. It had 54 items, which included the personal protective equipment and used materials, disinfection of the driver's cabin, equipment, and the patient care cabin. The minimum agreement obtained was 85% and the mean of the Content Validation Index was 0.96. CONCLUSION: The checklist was considered valid in terms of content and can be used to disinfect ambulances transporting patients with Covid-19.