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The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19 donor lungs with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage (DAD). We identify changes in cellular composition across progressive DAD, including waves of molecularly distinct macrophages and depleted epithelial and endothelial populations throughout different types of tissue damage. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early DAD, and fibrosis-related collagens in organised DAD. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early DAD. These results provide the first comprehensive, spatially resolved atlas of DAD stages, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways across alveolar damage progression.
Subject(s)
Fibrosis , Adenocarcinoma, Bronchiolo-Alveolar , COVID-19 , Respiratory InsufficiencyABSTRACT
PURPOSE: To define the impact of the COVID-19 outbreak on hospital surgical activity and assess the incidence of perioperative COVID-19 within two protocolized screening pathways for elective and non-elective surgery. METHODS: We conducted a prospective cohort study of adults undergoing surgery during the COVID-19 outbreak. The elective pathway included telephone surveys and a quantitative polymerase-chain-reaction test (RT-PCR) only for patients who were asymptomatic and at low risk of infection. Only patients with negative screening underwent surgery. In the non-elective pathway, preoperative screening was performed during the hospital admission. RESULTS: Among 835 patients considered for the elective pathway, 725 had negative RT-PCR results and underwent surgery. This reflects an 83% reduction in surgical activity from 2019. Moreover, 596 patients underwent non-elective surgery, representing a 28% reduction. Preoperatively, 39 patients (6.5%) tested positive for SARS-CoV-2 and underwent surgery through the non-elective pathway, vs. none in the elective pathway (p < 0.001). Postoperatively, 1.4% of elective surgery patients and 2.2% of non-elective surgery patients tested positive (p > 0.05). Mortality was higher in non-elective surgery (0.6% vs. 2.9%, p < 0.001) and in patients with COVID-19 (0% vs. 14%, p < 0.001). CONCLUSIONS: The low incidence of COVID-19 in elective surgeries during the outbreak demonstrates the importance and effectiveness of preoperative screening, combining surveys and RT-PCR.
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Introducción y objetivos: Analizar la evolución de los pacientes que padecen fibrilación auricular (FA) y diabetes a medio plazo en una situación de pandemia de la COVID-19 y describir su influencia en esta población. Métodos: Registro multicéntrico y prospectivo que incluyó a pacientes con FA y diabetes atendidos en consultas de cardiología. Se realizó un análisis multivariante para determinar las variables asociadas a la aparición de eventos clínicos y mortalidad. La inclusión se realizó en febrero-diciembre de 2019. Resultados: Se analizó la evolución de 633 pacientes, 96,2% de los incluidos en el registro REFADI durante un seguimiento medio de 835 días (edad media 73,8 ± 8,5 años, 54,3% varones, CHA2DS2-VASc 4,34 ± 1,4, HAS-BLED 2,47 ± 0,96). La proporción de pacientes anticoagulados se mantuvo constante (95,6 frente a 94,5%;p = 0,24). Hubo un descenso de antagonistas de la vitamina K (del 31,4 al 19,7%;p < 0,01), y un aumento de los anticoagulantes directos (del 62,0 al 70,3%;p < 0,01). Durante el seguimiento hubo un aumento en la prescripción de inhibidores SGLT2 (del 20,0 al 25,5%;p < 0,01) y agonistas GLP1 (del 4,2 al 9,1%;p < 0,01). Falleció el 17,2% de los pacientes, la mayoría de causa cardiovascular, 6,4% por COVID-19, 2,8% por ictus y 1,8% por hemorragia. La mayor edad, la menor fracción de eyección, los niveles más bajos de hemoglobina y especialmente la menor prescripción de anticoagulantes directos se asociaron con la mortalidad. Conclusiones: Los pacientes con FA y diabetes tienen un elevado riesgo tromboembólico y de sufrir complicaciones, sobre todo de origen cardiovascular.
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INTRODUCTION: Clefts of the lip are of the most common congenital craniofacial anomalies. The development and implementation of an enhanced recovery after surgery (ERAS) protocol among patients undergoing cleft lip repair may decrease postoperative complications, accelerate recovery, and result in earlier postoperative discharge. METHODS: A modified ERAS program was developed and applied through Global Smile Foundation outreach craniofacial programs. The main components of this protocol include: (1) preoperative patient education, (2) nutrition screening, (3) smoking cessation when applicable, (4) use of topical anesthetic adjuncts, (5) facial nerve blocks, (6) postoperative analgesia, (7) preferential use of short-acting narcotics, (8) antibiotic administration, (9) use of elbow restraints, (10) early postoperative oral feeding and hydration, and (11) discharge planning. RESULTS: Between April 2019 and March 2020, GSF operated on 126 patients with cleft lip from different age groups and 58.8% of them were less than 1 year of age. Three patients (2.4%) had delayed wound healing and one (0.8%) had postoperative bleeding. There were no cases of mortality, length of hospital stay did not exceed 1 postoperative day, and patients were able to tolerate fluids intake at discharge. CONCLUSION: The implementation of an ERAS protocol among patients undergoing cleft lip repair has shown to be highly effective in minimizing postoperative discomfort while reducing opioids use, decreasing the length of stay in hospital, and leading to early oral feeding resumption. The ERAS principles described carry increased relevance in the context of the ongoing COVID-19 pandemic and opioid crisis and can be safely applied in resource-constrained settings.
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Introduction: Articles published in the literature report neurological manifestations or "complications" of SARS-CoV-2 infection and conclude that the different neurological manifestations are relatively similar, but with different frequencies. This study aimed to determine the frequency of neurological manifestations of COVID-19 and to identify which are associated with mortality. Method(s): We performed a retrospective study of all patients diagnosed with SARS-CoV-2 infection by RT-PCR at Hospital 1degree de Octubre, in Mexico, from the beginning of the pandemic to 22 December 2020. A total of 561 patients were identified, 370 of whom presented neurological manifestations. Result(s): The global mortality rate was 37.8% (140/370), increasing to 92.4% among intubated patients (135/146). Of the 370 patients included, approximately 20% of neurological symptoms (headache, neurological impairment, anosmia, ageusia) accounted for 80% of cases of neurological manifestations. Conclusion(s): At our hospital, 80% of the patients with neurological manifestations of COVID-19 presented headache, neurological impairment, ageusia, and/or anosmia. Neurological impairment at admission or before arriving at hospital was identified as a risk factor for mortality.Copyright © 2021 Sociedad Espanola de Neurologia
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The COVID-19 pandemic affected the main Amazon cities dramatically, with Iquitos City reporting the highest seroprevalence of anti-SARS-CoV-2 antibodies during the first COVID-19 wave worldwide. This phenomenon raised many questions about the possibility of a co-circulation of dengue and COVID-19 and its consequences. We carried out a population-based cohort study in Iquitos, Peru. We obtained a venous blood sample from a subset of 326 adults from the Iquitos COVID-19 cohort (August 13-18, 2020) to estimate the seroprevalence of anti-dengue virus (DENV) and anti-SARS-CoV-2 antibodies. We tested each serum sample for anti-DENV IgG (serotypes 1, 2, 3, and 4) and SARS-CoV-2 antibodies anti-spike IgG and IgM by ELISA. We estimated an anti-SARS-CoV-2 seroprevalence of 78.0% (95% CI, 73.0-82.0) and an anti-DENV seroprevalence of 88.0% (95% CI, 84.0-91.6), signifying a high seroprevalence of both diseases during the first wave of COVID-19 transmission in the city. The San Juan District had a lower anti-DENV antibody seroprevalence than the Belen District (prevalence ratio, 0.90; 95% CI, 0.82-0.98). However, we did not observe these differences in anti-SARS-CoV-2 antibody seroprevalence. Iquitos City presented one of the highest seroprevalence rates of anti-DENV and anti-SARS-CoV-2 antibodies worldwide, but with no correlation between their antibody levels.
Subject(s)
COVID-19 , Adult , Humans , COVID-19/epidemiology , SARS-CoV-2 , Peru/epidemiology , Cohort Studies , Seroepidemiologic Studies , Pandemics , Antibodies, Viral , Immunoglobulin GABSTRACT
Background Elderly patients are more susceptible to Coronavirus Disease-2019 (COVID-19) and are more likely to develop it in severe forms, (e.g., Acute Respiratory Distress Syndrome [ARDS]). Prone positioning is a treatment strategy for severe ARDS;however, its response in the elderly population remains poorly understood. The main objective was to evaluate the predictive response and mortality of elderly patients exposed to prone positioning due to ARDS-COVID-19. Methods This retrospective multicenter cohort study involved 223 patients aged ≥ 65 years, who received prone position sessions for severe ARDS due to COVID-19, using invasive mechanical ventilation. The PaO2/FiO2 ratio was used to assess the oxygenation response. The 20-point improvement in PaO2/FiO2 after the first prone session was considered for good response. Data were collected from electronic medical records, including demographic data, laboratory/image exams, complications, comorbidities, SAPS III and SOFA scores, use of anticoagulants and vasopressors, ventilator settings, and respiratory system mechanics. Mortality was defined as deaths that occurred until hospital discharge. Results Most patients were male, with arterial hypertension and diabetes mellitus as the most prevalent comorbidities. The non-responders group had higher SAPS III and SOFA scores, and a higher incidence of complications. There was no difference in mortality rate. A lower SAPS III score was a predictor of oxygenation response, and the male sex was a risk predictor of mortality. Conclusion The present study suggests the oxygenation response to prone positioning in elderly patients with severe COVID-19-ARDS correlates with the SAPS III score. Furthermore, the male sex is a risk predictor of mortality.
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We present the software ModInterv as an informatics tool to monitor, in an automated and user-friendly manner, the evolution and trend of COVID-19 epidemic curves, both for cases and deaths. The ModInterv software uses parametric generalized growth models, together with LOWESS regression analysis, to fit epidemic curves with multiple waves of infections for countries around the world as well as for states and cities in Brazil and the USA. The software automatically accesses publicly available COVID-19 databases maintained by the Johns Hopkins University (for countries as well as states and cities in the USA) and the Federal University of Viçosa (for states and cities in Brazil). The richness of the implemented models lies in the possibility of quantitatively and reliably detecting the distinct acceleration regimes of the disease. We describe the backend structure of software as well as its practical use. The software helps the user not only to understand the current stage of the epidemic in a chosen location but also to make short term predictions as to how the curves may evolve. The app is freely available on the internet (http://fisica.ufpr.br/modinterv), thus making a sophisticated mathematical analysis of epidemic data readily accessible to any interested user.
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COVID-19 has serious effects on cardiorespiratory capacity. In this sense, physical activity has been identified as beneficial in the treatment of cardiorespiratory diseases due to its anti-inflammatory and immunosuppressive benefits. To date, no study has been found on cardiorespiratory capacity and rehabilitation in patients cured after COVID-19. Thus, this brief report aims to relate the benefits of physical activity to cardiorespiratory function after COVID-19. It is important to know how different levels of physical activity can be related to the different symptoms of COVID-19. In view of this, the objectives of this brief report were to: (1) explore the theoretical associations between COVID-19 symptoms and physical activity;(2) compare the cardiorespiratory function of non-COVID-19 participants and post-COVID-19 patients;and (3) propose a physical activity program to improve the cardiorespiratory fitness of post-COVID-19 patients. Thus, we note that moderate-intensity physical activity (i.e., walking) has a greater beneficial effect on immune function, whereas vigorous activity (i.e., marathon running) tends to temporarily reduce immune function through an imbalance of cytokine types I and II in the hours and days after exercise. However, there is no consensus in the literature in this regard, since other investigations suggest that high-intensity training can also be beneficial, not causing clinically relevant immunosuppression. Physical activity has been shown to be beneficial in improving the clinical conditions most frequently associated with severe COVID-19. Thus, it is possible to infer that physically active individuals seem to be less exposed to the dangers of severe COVID-19 compared to non-active individuals through the benefits of physical activity in strengthening the immune system and fighting infections. The current study demonstrates that physical activity appears to be beneficial in improving the clinical conditions most often associated with severe COVID-19.
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Introduction: Olfactory loss is prevalent in SARS-CoV-2 infected patients. Some therapies have been tested to help patients, but both time to symptom recovery and prevalence of full recovery are unknown, and prospective studies testing any method of therapy are rare. Objective(s): Compare olfactory training effectivity in improving smell sense in COVID-19 patients with olfactory loss after acute disease. Method(s): subjects that had olfactory loss during confirmed COVID-19 performed Connecticut Chemosensory Clinical Research Center olfactory test. Those who presented with some grade of olfactory loss were invited to participate this trial, in which they were randomized in 2 groups (olfactory training versus a control group with olfactory training without smell sensation). Patients were evaluated monthly until full olfactory recovery or until 6 months of follow-up. Result(s): among 182 individuals, 149 presented with abnormal olfactory test. 123 patients finished the study (treatment: n=68;control: n=55). Both groups showed olfactory improvement along the follow-up period with significant statistical difference until the second reevaluation (1st-2nd test: p<.001;2nd-3rd test: p<.001;3rd-4th test: p=.08;4th-5th test: p=1;5th-6th test: p=1;6th-7th test: p=1). Olfactory test was significant better at control group at the beginning (p=.001) and persisted until the second reevaluation (p=.004 and p=.009, respectively), in which treatment group had similar test results (p>.05). Conclusion(s): Olfactory training demonstrated good results as treatment modality after COVID-19 smell loss, with significant improvement after 70 days of therapy.
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Introduction: Olfactory disfunction is a common marker for COVID-19 phenotype, mainly, during its acute phase. However, olfactory recovery is a controversial issue which requires further investigation. Objective(s): Verify olfactory dysfunction in health care workers with COVID-19 according to individual perception and Connecticut Chemosensory Clinical Research Center olfactory test (CCCRC OT). Method(s): A cross-sectional study was conducted in health care workers positive for SARS-CoV-2 RT-PCR or serological tests who perceived olfactory dysfunction. Epidemiological and clinical data were extracted, as well as time from loose, test and recovery of olfaction;and the degree of olfactory dysfunction was assessed using individual perception and CCCRC OT. Result(s): A total of 173 participants were included. CCCRC OT was performed approximately 45 days (45.08+/-20.21) after positive test. Participants were allocated into two groups according to CCCRC OT: (G1) 33/173 [19.1%] normal sense of smell;(G2) 140/173 [80.9%] altered sense of smell. The mean time of olfactory dysfunction was lower in the G1 than G2 group (9.42+/-4.99 days vs. 17.14+/- 3.74 days;P<.001);while there were no differences in the other measured moments. Full recovery was reported by 66 (38.2%) individuals, but only 33 (19.1%) individuals showed normal results at CCCRC OT. Conclusion(s): Time for initial olfactory recovery after SARS-CoV-2 infection has proved to be the best prognostic factor for complete recovery. Also, olfactory objective tests are essential for reliable assessment.
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BACKGROUND: Elderly patients are more susceptible to Coronavirus Disease-2019 (COVID-19) and are more likely to develop it in severe forms, (e.g., Acute Respiratory Distress Syndrome [ARDS]). Prone positioning is a treatment strategy for severe ARDS; however, its response in the elderly population remains poorly understood. The main objective was to evaluate the predictive response and mortality of elderly patients exposed to prone positioning due to ARDS-COVID-19. METHODS: This retrospective multicenter cohort study involved 223 patients aged ≥ 65 years, who received prone position sessions for severe ARDS due to COVID-19, using invasive mechanical ventilation. The PaO2/FiO2 ratio was used to assess the oxygenation response. The 20-point improvement in PaO2/FiO2 after the first prone session was considered for good response. Data were collected from electronic medical records, including demographic data, laboratory/image exams, complications, comorbidities, SAPS III and SOFA scores, use of anticoagulants and vasopressors, ventilator settings, and respiratory system mechanics. Mortality was defined as deaths that occurred until hospital discharge. RESULTS: Most patients were male, with arterial hypertension and diabetes mellitus as the most prevalent comorbidities. The non-responders group had higher SAPS III and SOFA scores, and a higher incidence of complications. There was no difference in mortality rate. A lower SAPS III score was a predictor of oxygenation response, and the male sex was a risk predictor of mortality. CONCLUSION: The present study suggests the oxygenation response to prone positioning in elderly patients with severe COVID-19-ARDS correlates with the SAPS III score. Furthermore, the male sex is a risk predictor of mortality.
Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Male , Aged , Female , Prone Position/physiology , Cohort Studies , Respiratory Distress Syndrome/therapy , Respiration, Artificial/adverse effects , Respiration, Artificial/methods , AgingABSTRACT
A generalized pathway model, with time-dependent parameters, is applied to describe the mortality curves of the COVID-19 disease for several countries that exhibit multiple waves of infections. The pathway approach adopted here is formulated explicitly in time, in the sense that the model's growth rate for the number of deaths or infections is written as an explicit function of time, rather than in terms of the cumulative quantity itself. This allows for a direct fit of the model to daily data (new deaths or new cases) without the need of any integration. The model is applied to COVID-19 mortality curves for ten selected countries and found to be in very good agreement with the data for all cases considered. From the fitted theoretical curves for a given location, relevant epidemiological information can be extracted, such as the starting and peak dates for each successive wave. It is argued that obtaining reliable estimates for such characteristic points is important for studying the effectiveness of interventions and the possible negative impact of their relaxation, as it allows for a direct comparison of the time of adoption/relaxation of control measures with the peaks and troughs of the epidemic curve.
ABSTRACT
COVID-19 has serious effects on cardiorespiratory capacity. In this sense, physical activity has been identified as beneficial in the treatment of cardiorespiratory diseases due to its anti-inflammatory and immunosuppressive benefits. To date, no study has been found on cardiorespiratory capacity and rehabilitation in patients cured after COVID-19. Thus, this brief report aims to relate the benefits of physical activity to cardiorespiratory function after COVID-19. It is important to know how different levels of physical activity can be related to the different symptoms of COVID-19. In view of this, the objectives of this brief report were to: (1) explore the theoretical associations between COVID-19 symptoms and physical activity; (2) compare the cardiorespiratory function of non-COVID-19 participants and post-COVID-19 patients; and (3) propose a physical activity program to improve the cardiorespiratory fitness of post-COVID-19 patients. Thus, we note that moderate-intensity physical activity (i.e., walking) has a greater beneficial effect on immune function, whereas vigorous activity (i.e., marathon running) tends to temporarily reduce immune function through an imbalance of cytokine types I and II in the hours and days after exercise. However, there is no consensus in the literature in this regard, since other investigations suggest that high-intensity training can also be beneficial, not causing clinically relevant immunosuppression. Physical activity has been shown to be beneficial in improving the clinical conditions most frequently associated with severe COVID-19. Thus, it is possible to infer that physically active individuals seem to be less exposed to the dangers of severe COVID-19 compared to non-active individuals through the benefits of physical activity in strengthening the immune system and fighting infections. The current study demonstrates that physical activity appears to be beneficial in improving the clinical conditions most often associated with severe COVID-19.
Subject(s)
COVID-19 , Cardiorespiratory Fitness , Humans , Physical Fitness/physiology , Exercise/physiology , ImmunityABSTRACT
We present the software ModInterv as an informatics tool to monitor, in an automated and user-friendly manner, the evolution and trend of COVID-19 epidemic curves, both for cases and deaths. The ModInterv software uses parametric generalized growth models, together with LOWESS regression analysis, to fit epidemic curves with multiple waves of infections for countries around the world as well as for states and cities in Brazil and the USA. The software automatically accesses publicly available COVID-19 databases maintained by the Johns Hopkins University (for countries as well as states and cities in the USA) and the Federal University of Viçosa (for states and cities in Brazil). The richness of the implemented models lies in the possibility of quantitatively and reliably detecting the distinct acceleration regimes of the disease. We describe the backend structure of software as well as its practical use. The software helps the user not only to understand the current stage of the epidemic in a chosen location but also to make short term predictions as to how the curves may evolve. The app is freely available on the internet (http://fisica.ufpr.br/modinterv), thus making a sophisticated mathematical analysis of epidemic data readily accessible to any interested user.
ABSTRACT
Background Retinoscopy is one of the most effective objective techniques for evaluating refractive status, especially in non-cooperative patients. However, it presents a slow learning curve that often leads to student frustration. With the current Covid-19 pandemic and the need for social isolation, clinical education based on simulation has become more relevant. Therefore, we implemented retinoscopy laboratories and learning protocols to reduce student stress and learning time. Methods We conducted a study to evaluate the retinoscopy learning curve using a new training protocol proposal. One hundred trainees were assessed in four stages, corresponding to 08, 12, 16, and 20 hours of training. Six different refractive defects were used trying to reproduce frequent conditions of care. The time spent on the assessment was not considered as additional training time. To analyze the data, we used non-parametric statistics and linear regression to assess the variables associated with training time and performance rate. Results The mean performance score at 08 hrs was 32.49% (±16.69 SD); at 12 hrs was 59.75% (±18.80 SD); at 16 hrs was 70.83% (±18.53 SD) and at 20 hrs was 84.26% (±13.18 SD). Performance at 12 hrs was significative higher than 08 hrs of training, but did not show significant differences with the performance rate at 16 and 20 hrs. We found a strong positive correlation between performance and training time in retinoscopy (R = 0.9773, CI: 0.2678 - 0.9995 p = 0.0227). Conclusion This study showed that an increasing number of hours of practice positively correlates with performance in retinoscopy. The elaboration of a protocol and standardization of performance per hour also allowed us to estimate that a minimum of 13.4 hrs of practice is required to achieve 60% performance. Using the resulting formula, it is possible to determine the number of hours of retinoscopy practice are necessary to reach a certain level of performance.