Objective: To compare the effects of a home-based pulmonary rehabilitation (PR) program with and without telecoaching on health-related outcomes in COVID-19 survivors. Methods: A total of 42 COVID-19 patients who completed medical treatment were randomly divided into two groups: the study (telecoaching) group (n = 21) and the control (no telecoaching) group (n = 21). Both groups participated in an 8-week home-based PR program including education, breathing exercises, strength training, and regular walking. The study group received phone calls from a physiotherapist once a week. Both groups of patients were assessed before and after the program by means of the following: pulmonary function tests; the modified Medical Research Council dyspnea scale; the six-minute walk test; extremity muscle strength measurement; the Saint George's Respiratory Questionnaire (to assess disease-related quality of life); the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36, to assess overall quality of life); and the Hospital Anxiety and Depression Scale. Results: In both groups, there were significant improvements in the following: FVC; the six-minute walk distance; right and left deltoid muscle strength; Saint George's Respiratory Questionnaire activity domain, impact domain, and total scores; and SF-36 social functioning, role-physical, role-emotional, and bodily pain domain scores (p < 0.05). Decreases in daily-life dyspnea, exertional dyspnea, and exertional fatigue were significant in the study group (p < 0.05), and the improvement in SF-36 social functioning domain scores was greater in the study group (p < 0.05). Conclusions: A home-based PR program with telecoaching increases social functioning and decreases daily-life dyspnea, exertional dyspnea, and exertional fatigue in COVID-19 survivors in comparison with a home-based PR program without telecoaching.

Keywords: COVID-19; Exercise; Telerehabilitation; Dyspnea; Fatigue.

Objective: To evaluate clinical outcomes and factors associated with mortality, focusing on secondary infections, in critically ill patients with COVID-19 in three Brazilian hospitals during the first pandemic wave. Methods: This was a retrospective observational study involving adult patients with COVID-19 admitted to one of the participating ICUs between March and August of 2020. We analyzed clinical features, comorbidities, source of SARS-CoV-2 infection, laboratory data, microbiology data, complications, and causes of death. We assessed factors associated with in-hospital mortality using logistic regression models. Results: We included 645 patients with a mean age of 61.4 years. Of those, 387 (60.0%) were male, 12.9% (83/643) had undergone solid organ transplant, and almost 10% (59/641) had nosocomial COVID-19 infection. During ICU stay, 359/644 patients (55.7%) required invasive mechanical ventilation, 225 (34.9%) needed renal replacement therapy, 337 (52.2%) received vasopressors, and 216 (33.5%) had hospital-acquired infections (HAIs), mainly caused by multidrug-resistant gram-negative bacteria. HAIs were independently associated with a higher risk of death. The major causes of death were refractory shock and multiple organ dysfunction syndrome but not ARDS, as previously reported in the literature. Conclusions: In this study, most of our cohort required invasive mechanical ventilation and almost one third had HAIs, which were independently associated with a higher risk of death. Other factors related to death were Charlson Comorbidity Index, SOFA score at admission, and clinical complications during ICU stay. Nosocomial COVID-19 infection was not associated with death. The main immediate causes of death were refractory shock and multiple organ dysfunction syndrome.

Keywords: COVID-19/mortality; Sepsis; Multiple organ failure.

Objective: To evaluate the performance of lung ultrasound to determine short-term outcomes of patients with COVID-19 admitted to the intensive care unit. Methods: This is a Prospective, observational study. Between July and November 2020, 59 patients were included and underwent at least two LUS assessments using LUS score (range 0-42) on day of admission, day 5th, and 10th of admission. Results: Age was 66.5±15 years, APACHE II was 8.3±3.9, 12 (20%) patients had malignancy, 46 (78%) patients had a non-invasive ventilation/high-flow nasal cannula and 38 (64%) patients required mechanical ventilation. The median stay in ICU was 12 days (IQR 8.5-20.5 days). ICU or hospital mortality was 54%. On admission, the LUS score was 20.8±6.1; on day 5th and day 10th of admission, scores were 27.6±5.5 and 29.4±5.3, respectively (P=0.007). As clinical condition deteriorated the LUS score increased, with a positive correlation of 0.52, P <0.001. Patients with worse LUS on day 5th versus better score had a mortality of 76% versus 33% (OR 6.29, 95%CI 2.01-19.65, p. 0.003); a similar difference was observed on day 10. LUS score of 5th day of admission had an area under the curve of 0.80, best cut-point of 27, sensitivity and specificity of 0.75 and 0.78 respectively. Conclusion: These findings position LUS as a simple and reproducible method to predict the course of COVID-19 patients.

Keywords: Lund diseases; COVID-19; Ultrasonography.

Objective: Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19. Methods: This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls. Results: A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = -0.01 (95% CI, -0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, -0.08 to 0.01]; p = 0.09). Conclusions: The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.

Keywords: Antiviral agents; COVID-19; SARS-CoV-2.

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])

Keywords: COVID-19; COVID-19/pathology; Pulmonary fibrosis; Respiratory function tests; Biopsy.

Objective: To answer questions related to the use of anticoagulants in the treatment of COVID-19 patients. Methods: This was a systematic review and meta-analysis of phase 3 randomized controlled trials comparing the use of anticoagulants in non-hospitalized and hospitalized COVID-19 patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to January 22, 2022. The risk of bias was assessed by the Cochrane risk-of-bias tool, and the quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation system. Results: A total of 401 studies were initially selected. Of those, 9 met the inclusion criteria and were therefore analyzed (a total of 6,004 patients being analyzed). In non-hospitalized COVID-19 patients, no significant difference was found between post-discharge prophylactic anticoagulation and no intervention regarding venous thromboembolism or bleeding at 30 days. In hospitalized COVID-19 patients, full anticoagulation resulted in a slight reduction in thrombotic events at 30 days (risk difference, -0.03; 95% CI, -0.06 to -0.00; p = 0.04; I2 = 78%), the quality of evidence being moderate. However, no significant difference was found between full anticoagulation and no intervention regarding the risk of major bleeding, the quality of evidence being very low. No significant difference was found between intermediate- and standard-dose prophylactic anticoagulation (risk difference, -0.01; 95% CI, -0.07 to 0.06; p = 0.81; I2 = 0%), the quality of evidence being very low. Conclusions: Therapeutic anticoagulation appears to have no effect on mortality in COVID-19 patients, resulting in a slight reduction in venous thromboembolism in hospitalized patients.

Keywords: Anticoagulants; COVID-19; SARS-CoV-2.

Objective: The present study aimed to assess the functional status of children diagnosed with COVID-19 at the time of hospitalization and the associations with clinical features. Methods: This prospective cohort study was carried out with children diagnosed with COVID-19 admitted to a tertiary hospital. The patients' functioning was assessed using the pediatric Functional Status Scale (FSS). Results: A total of 62 children with a median age of 3 years old were included in the study, and 70% had some comorbidity prior to the diagnosis of COVID-19. The median length of stay was nine days, during which period five patients died. The FSS assessment of the sample showed that approximately 55% had some functional alteration. The group of patients with the highest FSS scores presented a lengthier hospital stay (p = 0.016), required more oxygen therapy (p < 0.001), mechanical ventilation (p = 0.001), and intensive care unit admissions (p = 0.019), and had more cardiac (p = 0.007), neurological (p = 0.003), and respiratory (p = 0.013) comorbidities. In the multivariate analysis, there was an association between the dependent variable length of stay and the total FSS score (b = 0.349, p = 0.004) and the presence of comorbidities (b = 0.357, p = 0.004). Conclusions: We observed that more than half of the children hospitalized due to COVID-19 had some level of functional change. Greater alterations in functional status were associated with the presence of previous comorbidities, a greater need for ventilatory support, and longer hospital stays.

Keywords: COVID-19, coronavirus, pediatrics, physical functional performance, functional status.

Objective: COVID-19 has been associated with a significant burden to those who survive the acute phase. We aimed to describe the quality of life and symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) at 90 days after hospital discharge of COVID-19 patients. Methods: Patients with COVID-19 admitted to a private hospital in the city of São Paulo, Brazil, between April of 2020 and April of 2021 were interviewed by telephone at 30 and 90 days after discharge to assess the quality of life and symptoms of depression, anxiety, and PTSD. Results: A total of 2,138 patients were included. The mean age was 58.6 ± 15.8 years, and the median length of hospital stay was 9.0 (5.0-15.8) days. Between the two time points, depression increased from 3.1% to 7.2% (p < 0.001), anxiety increased from 3.2% to 6.2% (p < 0.001), and PTSD increased from 2.3% to 5.0% (p < 0.001). At least one physical symptom related to COVID-19 diagnosis persisted in 32% of patients at day 90. Conclusions: Persistence of physical symptoms was high even at 90 days after discharge. Although the prevalence of symptoms of anxiety, depression, and PTSD was low, these symptoms persisted for three months, with a significant increase between the time points. This finding indicates the need to identify at-risk patients so that they can be given an appropriate referral at discharge.

Keywords: COVID-19; Anxiety; Depression; Stress disorders, post-traumatic; Quality of life; Critical care outcomes.

Objective: Currently, little is known about the long-term outcomes of COVID-19 in the pediatric population. The aim of this study was to investigate the long-term clinical outcomes of pediatric patients hospitalized with COVID-19. Methods: This was a prospective cohort study involving unvaccinated children and adolescents admitted to a tertiary hospital in southern Brazil with a COVID-19 diagnosis. Data were collected from electronic medical records for one year after the diagnosis. Results: A total of 66 children were included: the median age was 2.9 years; 63.6% were male; and 48.5% were under 2 years of age. Over 70% had at least one comorbidity prior to the COVID-19 diagnosis. During the one-year follow-up period, 59.1% of the children revisited the emergency department, 50% required readmission, and 15.2% died. Younger children with longer hospital stays were found to be at greater risk of readmission. Having cancer and impaired functionality were found to increase the risk of death within one year. Conclusions: Our findings indicate that most children hospitalized with COVID-19 have comorbidities. Younger age at admission and a longer hospital stay seem to be risk factors for readmission. In addition, the presence of cancer and impaired functionality are apparently associated with the poor outcome of death within the first year after the diagnosis of COVID-19.

Keywords: COVID-19; Pediatrics; Physical functional performance.

Objective: To assess the influence of the COVID-19 pandemic on hospital admissions (HA), intra-hospital deaths (HD), and intra-hospital lethality rates (HL) related to respiratory diseases (RD) other than COVID-19 in Brazil. Methods: This observational time-series study was conducted through comparative analyses of the HA, HD, and HL related to non-COVID-19 RD registered between March and December 2020 by the Brazilian Unified Public Health System on the DataSUS Tabnet platform, using as reference the values recorded in the same period of 2019 and those projected by linear regression methods for 2020, considering the period from 2015 to 2019. The adopted statistical significance level was 5% (p < 0.05). Results: Compared to 2019, in 2020, there was a 42% decrease in HA and a 7.4% decrease in total HD related to non-COVID-19 RD, followed by a 60% increase in HL associated with this group of diseases. The HA and HL registered in 2020 differed significantly from the projected trend for that year by linear regression (p < 0.05). Of note, a significant reduction in hospitalizations due to asthma (-46%), chronic obstructive pulmonary disease (-45%), bronchiectasis (-54%), pneumonia (-46%), and acute bronchitis (-73%) was observed. Conclusions: During the first 8 months of the pandemic, there was a decline in HA and an increase in HL related to non-COVID-19 RD in Brazil, which can hypothetically reflect logistical challenges and delays in the management of this group of diseases.

Keywords: Pulmonary disease, COVID-19, non-COVID-19, Hospitalization, Mortality.

Objective: Chloroquine or hydroxychloroquine has demonstrated no effect on the treatment of hospitalized COVID-19 patients. This study aimed to answer questions related to the use of hydroxychloroquine for pre-exposure or post-exposure prophylaxis of SARS-CoV-2 infection and in the treatment of patients with mild COVID-19 in terms of hospitalization, adverse events, and mortality. Methods: This was a systematic review and meta-analysis of phase 3 randomized clinical trials, selected from various databases, which compared patients who received hydroxychloroquine for SARS-CoV-2 prophylaxis or treatment of mild COVID-19 cases with controls. Results: A total number of 1,376 studies were retrieved. Of those, 9 met the eligibility criteria and were included in the study. No statistically significant differences were found between the hydroxychloroquine and control groups in terms of pre- or post-exposure prophylaxis of SARS-CoV-2 infection. The use of hydroxychloroquine increased the risk of adverse events by 12% (95% CI, 6-18%; p < 0.001), and the number needed to harm was 9. In addition, no significant differences were found between the hydroxychloroquine and control groups regarding hospitalization (risk difference [RD] = -0.02; 95% CI, -0.04 to 0.00; p = 0.14) or mortality (RD = 0.00; 95% CI, -0.01 to 0.02; p = 0.98) in the treatment of mild COVID-19. Conclusions: The use of hydroxychloroquine for prophylaxis of SARS-CoV-2 infection or treatment of patients with mild COVID-19 is not recommended.

Keywords: Hydroxychloroquine; COVID-19; SARS-CoV-2.