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Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

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INTRODUCCIÓN: En Chile, los virus respiratorios son una causa frecuente de neumonía adquirida en la comunidad (NAC), con admisión a unidades de paciente crítico en adultos. Los agentes etiológicos asociados son influenza A y B, virus respiratorio sincicial (VRS) y Hantavirus, sumándose el SARS-CoV-2 desde 2020. OBJETIVO: Identificar variables clínicas y de laboratorio asociadas a mortalidad a 30 días en NAC virales graves en un centro del sur de Chile. Metodología: Estudio observacional, se agruparon dos cohortes de pacientes con NAC grave según criterio IDSA/ATS (años 2013-2018, "No COVID-19") y año 2020 ("COVID-19"). Se recolectaron datos sociodemográficos, clínica, laboratorio y mortalidad a 30 días. Se utilizaron pruebas de Chi-cuadrado y Prueba t- student, para variables categóricas y continuas respectivamente. La mortalidad se evaluó mediante regresión logística binaria, con resultados reportados como Odd ratios (ORs). RESULTADOS: La mortalidad a 30 días fue: Hanta virus 54.5%, H1N1 36,8%, 30,4% otras influenza, 25% VRS y 23,6% para COVID-19. Sin diferencia significativa entre el tipo de virus (COVID-19 o NO COVID-19). La mortalidad se asoció con edad > 65 años (OR: 4,6; p 65 años, inmunosupresión, cianosis y uremia al ingreso se asociaron con mayor mortalidad a 30 días en los ingresos por NAC viral grave.

INTRODUCTION: Severe community-acquired pneumonia (CAP) due to respiratory viruses is highly prevalent in Chile. Common etiologies include Influenza A and B, respiratory syncytial virus (RSV), Hantavirus, and SARS-CoV-2 since 2020. OBJECTIVE: To identify clinical and laboratory features associated with 20-day mortality in severe viral CAP in a high complexity health care center in southern Chile. METHODS: The observational study included two cohorts of patients with severe CAP according to IDSA/ATS criteria: the years 2013-2018 (No COVID-19) and the year 2020 (COVID-19). Sociodemographic, clinical, laboratory, and 30-day mortality data were collected. We used Chi-square and Student's T for categorical and continuous variables. We used a binary logistic regression model for mortality analysis, reporting the results as Odd ratios (ORs). RESULTS: Mortality at 30 days was: Hantavirus 54.4%, Influenza H1N1 36.8%, other influenza 30.4%, RSV 25%, and COVID-19 23.6%. We found no significant difference regarding type of virus (COVID-19 or NO COVID-19). Mortality was associated with older age (OR: 4.6; p-value < 0.01), immunosuppression (OR: 5.8; p-value 0.01), and cyanosis (OR: 3.8, p-value 0.02). Conclusion: COVID-19 was not associated with an increased risk of 30-day mortality compared to other common respiratory viruses in our study. Older age, immunosuppression, and cyanosis were associated with higher risk among patients with severe viral CAP.

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INTRODUCTION: Severe community-acquired pneumonia (CAP) due to respiratory viruses is highly prevalent in Chile. Common etiologies include Influenza A and B, respiratory syncytial virus (RSV), Hantavirus, and SARS-CoV-2 since 2020. OBJECTIVE: To identify clinical and laboratory features associated with 20-day mortality in severe viral CAP in a high complexity health care center in southern Chile. METHODS: The observational study included two cohorts of patients with severe CAP according to IDSA/ATS criteria: the years 2013-2018 (No COVID-19) and the year 2020 (COVID-19). Sociodemographic, clinical, laboratory, and 30-day mortality data were collected. We used Chi-square and Student's T for categorical and continuous variables. We used a binary logistic regression model for mortality analysis, reporting the results as Odd ratios (ORs). RESULTS: Mortality at 30 days was: Hantavirus 54.4%, Influenza H1N1 36.8%, other influenza 30.4%, RSV 25%, and COVID-19 23.6%. We found no significant difference regarding type of virus (COVID-19 or NO COVID-19). Mortality was associated with older age (OR: 4.6; p-value < 0.01), immunosuppression (OR: 5.8; p-value 0.01), and cyanosis (OR: 3.8, p-value 0.02). CONCLUSION: COVID-19 was not associated with an increased risk of 30-day mortality compared to other common respiratory viruses in our study. Older age, immunosuppression, and cyanosis were associated with higher risk among patients with severe viral CAP.

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Objective: To determine the association between Obstructive Sleep Apnea (OSA) with long-term symptoms and inflammatory cytokines, exploring the changes between 4-months and 1-year after COVID-19 infection. Methods: We conducted an observational, prospective cohort study, including patients ≥18 years old with confirmed diagnosis of COVID-19 between April to July 2020. All participants underwent two clinical follow-up visits, the first at 4-months (Visit 1) and the second at 1 year, after SARS-CoV-2 infection (Visit 2). Plasma glucose, total cholesterol, HDL, and triglycerides. Regarding pulmonary function, spirometry and lung diffusion capacity tests were assessed. For mental and neurocognitive evaluation, a short-form (SF-12), Beck depression and Hospital-Anxiety depression questionnaires were conducted at both time-points, whereas the Montreal Cognitive assessment was conducted during the second follow-up. Regarding to sleep evaluation, Epworth Sleepiness Scale, Insomnia Severity index and STOP-BANG questionnaire were conducted. Additionally, a home sleep apnea test and 7-day wrist actigraphy were performed in all participants. Inflammatory cytokines were measured using an inflammatory cytokine bead array kit. p-values < 0.05 were considered statistically significant and statistical analyses were performed using R software. Results: A total of 60 patients were included in the first follow-up, from which 57 completed the second follow-up. The mean age was 46.4 years-old (SD ± 13.1) and 53.3% were male. 30% of cases reported mild COVID-19 infection, 28.3% with moderate illness, and 41.6% with severe illness. Moreover, 56.6% of them were admitted to the ICU. Regarding to metabolic values, the OSA group showed higher values of insulin resistance (IR) (27%), systolic blood pressure (SBP) 135.2 (±19.1), dyslipidemia (67.5%), total cholesterol 202.1 (±60.5), triglycerides 176.1 (±119.0) and HOMA-IR 9.0 (±18.8) in comparison with the non-OSA group. 1 year after COVID-19 infection, DLCO test remains abnormal in OSA patients (25% OSA vs. 3.6% non-OSA, p = 0.02). Finally, those participants with OSA who develop ARDS reported an adjusted OR 20.4 (95%-CI, 1.04-504) risk of neurocognitive impairment. Discussion: Among patients with previous COVID-19, OSA impact the development of incident glycemic, neurocognitive impairment, and abnormal functional pulmonary changes that persist up to 1 year since acute phase.

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BACKGROUND: Long term sequelae can be observed after SARS-CoV2. AIM: To describe the sexual, physical, mental and sleep sequelae four months after SARS-CoV2 diagnosis. PATIENTS AND METHODS: Patients recovering from SARS-CoV2 with different degrees of disease severity were consecutively included and separated in two study groups, namely Group 1 including patients that had an acute respiratory distress syndrome (ARDS) and Group 2 including those with mild or moderate COVID-19. Handgrip strength, respiratory polygraphy (RP), Quality of life using the SF-12 questionnaire, and the international index of erectile (IIEF-5) function were assessed. RESULTS: Twenty patients who had ARDS, and 10 without ARDS were included. Erectile dysfunction was observed in 77 and 10% of patients with and without ARDS, respectively (p < 0.01). The figures for sleep obstructive apnea were 82 and 40% respectively (p = 0.02) and for the physical domain SF-12 score were 39.2 and 47.9 points respectively (p = 0.01). No differences in muscle strength were observed. After a multivariable analysis, previous ARDS due to COVID-19 was independently associated with erectile dysfunction, with an odds ratio of 30.6 (95% confidence intervals, 3.08300.3, p = 0.003). CONCLUSIONS: Among men with ARDS due to COVID-19, the prevalence of erectile dysfunction was high and independently associated with a severe disease four months after discharge.

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OBJECTIVE: To describe the prevalence and severity of sleep disorders and circadian alterations in COVID-19 patients four months after the acute phase of the disease. METHODS: This was a cross-sectional observational prospective study of patients with mild COVID-19, moderate COVID-19 (requiring hospitalization but no mechanical ventilation), or severe COVID-19 (with ARDS) four months after the acute phase of the disease. All patients underwent a home sleep apnea test and seven-day wrist actigraphy, as well as completing questionnaires to assess sleep quality and mental health. Differences among the three groups of patients were evaluated by ANOVA and the chi-square test. RESULTS: A total of 60 patients were included in the study. Of those, 17 were in the mild COVID-19 group, 18 were in the moderate COVID-19 group, and 25 were in the severe COVID-19 group. Sleep quality, as assessed by satisfaction, alertness, timing, efficiency, and duration scale scores, was found to be impaired in all three groups, which also had a high prevalence of unhealthy sleep, as assessed by the Pittsburgh Sleep Quality Index. The prevalence of insomnia was increased in all three groups, as assessed by the Insomnia Severity Index. The home sleep apnea test showed that the overall prevalence of obstructive sleep apnea was 60%, and seven-day wrist actigraphy showed that total sleep time was < 7 h in all three groups. Changes in quality of life and in the circadian rest-activity pattern were observed in all three groups. CONCLUSIONS: Sleep-related symptoms, changes in the circadian rest-activity pattern, and impaired mental health appear to be common in COVID-19 patients four months after the acute phase of the disease, severe COVID-19 being associated with a higher prevalence of obstructive sleep apnea.

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BACKGROUND: COVID-19 infection can be especially severe in certain risk populations such as patients with hematologic malignancies. Aim: To describe the characteristics and clinical outcomes of a population of patients with hematologic malignancies and COVID-19. MATERIAL AND METHODS: Review of medical records of patients with COVID-19 and hematologic malignancies, treated in Hematology Service of a regional hospital in Chile, between April 1 and October 30, 2020. Demographic characteristics, chronic comorbidities and clinical characteristics related to the underlying disease and COVID-19 infection were recorded. Results: Thirty adults aged 17 to 73 years (67% men) with COVID-19 confirmed by RT-PCR, were evaluated. Forty percent had comorbidities, mainly hypertension (30%), obesity (27%) and diabetes (10%). Two thirds of cases came from a nosocomial outbreak and 77% were symptomatic. Half of the cases had mild disease and 20% required mechanical ventilation. Five patients (17%) died from COVID 19. Female sex, the presence of comorbidities and obesity were more common among deceased patients. Only 1 of 5 deceased patients were in complete remission. No differences were found in the mean survival according to requirement for intubation or the presence of complete remission. CONCLUSIONS: This population with hematologic malignancies and COVID-19 had special characteristics leading to a greater fatality rate which, in this series, does not increase with the use of mechanical ventilation.

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BACKGROUND: COVID-19 infection can be especially severe in certain risk populations such as patients with hematologic malignancies. AIM: To describe the characteristics and clinical outcomes of a population of patients with hematologic malignancies and COVID-19. MATERIAL AND METHODS: Review of medical records of patients with COVID-19 and hematologic malignancies, treated in Hematology Service of a regional hospital in Chile, between April 1 and October 30, 2020. Demographic characteristics, chronic comorbidities and clinical characteristics related to the underlying disease and COVID-19 infection were recorded. RESULTS: Thirty adults aged 17 to 73 years (67% men) with COVID-19 confirmed by RT-PCR, were evaluated. Forty percent had comorbidities, mainly hypertension (30%), obesity (27%) and diabetes (10%). Two thirds of cases came from a nosocomial outbreak and 77% were symptomatic. Half of the cases had mild disease and 20% required mechanical ventilation. Five patients (17%) died from COVID 19. Female sex, the presence of comorbidities and obesity were more common among deceased patients. Only 1 of 5 deceased patients were in complete remission. No differences were found in the mean survival according to requirement for intubation or the presence of complete remission. CONCLUSIONS: This population with hematologic malignancies and COVID-19 had special characteristics leading to a greater fatality rate which, in this series, does not increase with the use of mechanical ventilation.

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BACKGROUND: Long term sequelae can be observed after SARS-CoV2. AIM: To describe the sexual, physical, mental and sleep sequelae four months after SARS-CoV2 diagnosis. PATIENTS AND METHODS: Patients recovering from SARS-CoV2 with different degrees of disease severity were consecutively included and separated in two study groups, namely Group 1 including patients that had an acute respiratory distress syndrome (ARDS) and Group 2 including those with mild or moderate COVID-19. Handgrip strength, respiratory polygraphy (RP), Quality of life using the SF-12 questionnaire, and the international index of erectile (IIEF-5) function were assessed. RESULTS: Twenty patients who had ARDS, and 10 without ARDS were included. Erectile dysfunction was observed in 77 and 10% of patients with and without ARDS, respectively (p < 0.01). The figures for sleep obstructive apnea were 82 and 40% respectively (p = 0.02) and for the physical domain SF-12 score were 39.2 and 47.9 points respectively (p = 0.01). No differences in muscle strength were observed. After a multivariable analysis, previous ARDS due to COVID-19 was independently associated with erectile dysfunction, with an odds ratio of 30.6 (95% confidence intervals, 3.08300.3, p = 0.003). CONCLUSIONS: Among men with ARDS due to COVID-19, the prevalence of erectile dysfunction was high and independently associated with a severe disease four months after discharge.

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INTRODUCTION: Patients with severe COVID-19 develops an acute respiratory distress syndrome (ARDS), requiring admission to the intensive care unit. COVID-19 also reports an increased prevalence of comorbidities, similar to patients with Sleep disorder breathing (SDB). OBJECTIVES: To evaluate the association between undiagnosed SDB and the risk of ARDS and pulmonary abnormalities in a cohort of patients' survivors of COVID-19 between 3 and 6 months after diagnosis. METHODS: Prospective cohort study of patients who developed ARDS during hospitalization due to COVID-19 compared with a control group of patients who had COVID-19 with mild to moderate symptoms. All patients were evaluated between the 12th and 24th week after SARS-CoV-2 infection. The evaluation includes persistent symptoms, lung diffusing capacity of carbon monoxide (DLCO), chest CT scan and home sleep apnea test. SDB was diagnosed by the respiratory disturbance index ≥5 ev/h. The association between SDB and ARDS, the hazards of lung impairment and the hazard ratios (HR) were analyzed. RESULTS: A total of 60 patients were included (ARDS: 34 patients, Control: 26 patients). The mean follow-up was 16 weeks (range 12-24). ARDS reported a high prevalence of SDB (79% vs. 38% in control group). A total of 35% reported DLCO impairment, and 67.6% abnormal chest CT. SDB was independently associated to ARDS, OR 6.72 (CI, 1.56-28.93), p < 0.01, and abnormal Chest CT, HR 17.2 (CI, 1.68-177.4, p = 0.01). Besides, ARDS, days in mechanical ventilation, male gender were also associated with an increased risk of abnormal chest CT. CONCLUSION: Undiagnosed SDB is prevalent and independently associated with ARDS. In addition, undiagnosed SDB increased the hazard of abnormal Chest CT in the midterm. STUDY REGISTER: ISRCTN16865246.

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ABSTRACT Objective: To describe the prevalence and severity of sleep disorders and circadian alterations in COVID-19 patients four months after the acute phase of the disease. Methods: This was a cross-sectional observational prospective study of patients with mild COVID-19, moderate COVID-19 (requiring hospitalization but no mechanical ventilation), or severe COVID-19 (with ARDS) four months after the acute phase of the disease. All patients underwent a home sleep apnea test and seven-day wrist actigraphy, as well as completing questionnaires to assess sleep quality and mental health. Differences among the three groups of patients were evaluated by ANOVA and the chi-square test. Results: A total of 60 patients were included in the study. Of those, 17 were in the mild COVID-19 group, 18 were in the moderate COVID-19 group, and 25 were in the severe COVID-19 group. Sleep quality, as assessed by satisfaction, alertness, timing, efficiency, and duration scale scores, was found to be impaired in all three groups, which also had a high prevalence of unhealthy sleep, as assessed by the Pittsburgh Sleep Quality Index. The prevalence of insomnia was increased in all three groups, as assessed by the Insomnia Severity Index. The home sleep apnea test showed that the overall prevalence of obstructive sleep apnea was 60%, and seven-day wrist actigraphy showed that total sleep time was < 7 h in all three groups. Changes in quality of life and in the circadian rest-activity pattern were observed in all three groups. Conclusions: Sleep-related symptoms, changes in the circadian rest-activity pattern, and impaired mental health appear to be common in COVID-19 patients four months after the acute phase of the disease, severe COVID-19 being associated with a higher prevalence of obstructive sleep apnea.

RESUMO Objetivo: Descrever a prevalência e gravidade de transtornos do sono e alterações circadianas em pacientes com COVID-19 quatro meses depois da fase aguda da doença. Métodos: Estudo prospectivo observacional transversal com pacientes com COVID-19 leve, moderada (com necessidade de hospitalização, mas não de ventilação mecânica) ou grave (com SDRA) quatro meses depois da fase aguda da doença. Todos os pacientes foram submetidos a teste domiciliar de apneia do sono e actigrafia de sete dias, além de terem preenchido questionários para avaliar a qualidade do sono e a saúde mental. As diferenças entre os três grupos foram avaliadas por meio de ANOVA e teste do qui-quadrado. Resultados: Foram incluídos no estudo 60 pacientes. Destes, 17 eram do grupo COVID-19 leve, 18 do grupo COVID-19 moderada e 25 do grupo COVID-19 grave. A qualidade do sono, avaliada pela pontuação na escala satisfaction, alertness, timing, efficiency, and duration, foi prejudicada nos três grupos, que também apresentaram alta prevalência de sono não saudável, pelo Índice de Qualidade do Sono de Pittsburgh. A prevalência de insônia, avaliada pelo Insomnia Severity Index, foi elevada nos três grupos. O teste domiciliar de apneia do sono mostrou que a prevalência geral de apneia obstrutiva do sono foi de 60%, e a actigrafia de sete dias mostrou que o tempo total de sono foi < 7 h nos três grupos. Alterações da qualidade de vida e do padrão circadiano de atividade e repouso foram observadas nos três grupos. Conclusões: Sintomas relacionados ao sono, alterações do padrão circadiano de atividade e repouso e comprometimento da saúde mental parecem ser comuns em pacientes com COVID-19 quatro meses depois da fase aguda da doença, sendo a COVID-19 grave associada a uma maior prevalência de apneia obstrutiva do sono.

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BACKGROUND: Coronavirus disease 2019 (COVID-19) ranges from asymptomatic disease to respiratory failure and requires invasive mechanical ventilation (IMV). Data about the sequelae after infection are scarce. The study aims to describe the prevalence of symptoms, pulmonary function tests (PFTs), and radiological changes after four months of follow-up. METHODS: A prospective, cross-sectional, multicentre study was performed. Patients with different illness severities were consecutively included (mild; moderate: hospitalized without IMV; severe: hospitalized with IMV). Clinical variables, health-related quality of life (HRQoL), PFT (spirometry, diffusing capacity of the lungs for carbon monoxide (DLCO)), and (CT) scans of the chest were obtained. The association between the risk of sequelae (DLCO <80%) and altered CT was analysed using logistic regression adjusted for confounding variables. RESULTS: 60 patients (18 mild, 17 moderate, and 25 severe) were included. Fatigue was found in 11% of the mild, 47% of the moderate and 36% of the severe group. Altered DLCO (mild: 5.5%, moderate: 41%, severe: 28%, p < .05) and change in HRQoL (mild: 50%, moderate: 94%, severe: 60%), while the severe group showed a higher prevalence of altered CT (88% vs. 64%). Awake prone position (APP) and high-flow nasal cannula (HFNC) was independently associated with altered DLCO, Odds ratio (OR) 7.28 (CI, 1.10-47.81; p < .05), and altered CT, OR 9.50 (CI, 1.26-71.5; p < .05). Besides, prolonged time in IMV was associated with altered CT, OR 1.24 (CI, 1.05-1.46; p < .05). DISCUSSION: It is common to find sequelae in symptoms, radiology, and PFT. In our series, the use of APP+HFNC and days on IMV were associated with an increased risk of sequelae.

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