Typical phenotypes of patients with acute respiratory failure with and without COVID-19 and their relationship with outcomes: a cohort study / Fenótipos característicos em pacientes com insuficiência respiratória aguda com e sem COVID-19 e sua relação com os desfechos: um estudo de coorte

ABSTRACT Objective: To compare, within a cohort of patients with acute respiratory failure, the phenotypes of patients with and without COVID-19 in the context of the pandemic and evaluate whether COVID-19 is an independent predictor of intensive care unit mortality. Methods: This historical cohort study evaluated 1001 acute respiratory failure patients with suspected COVID-19 admitted to the intensive care unit of 8 hospitals. Patients were classified as COVID-19 cases and non-COVID-19 cases according to real-time polymerase chain reaction results. Data on clinical and demographic characteristics were collected on intensive care unit admission, as well as daily clinical and laboratory data and intensive care unit outcomes. Results: Although the groups did not differ in terms of APACHE II or SOFA scores at admission, the COVID-19 group had more initial symptoms of fever, myalgia and diarrhea, had a longer duration of symptoms, and had a higher prevalence of obesity. They also had a lower PaO2/FiO2 ratio, lower platelet levels than non-COVID-19 patients, and more metabolic changes, such as higher levels of blood glucose, C-reactive protein, and lactic dehydrogenase. Patients with non-COVID-19 acute respiratory failure had a higher prevalence of chronic obstructive pulmonary disease/asthma and cardiopathy. Patients with COVID-19 stayed in the hospital longer and had more complications, such as acute kidney failure, severe acute respiratory distress syndrome and severe infection. The all-cause mortality rate was also higher in this group (43.7% in the COVID-19 group versus 27.4% in the non-COVID-19 group). The diagnosis of COVID-19 was a predictor of intensive care unit mortality (odds ratio, 2.77; 95%CI, 1.89 - 4.07; p < 0.001), regardless of age or Charlson Comorbidity Index score. Conclusion: In a prospective cohort of patients admitted with acute respiratory failure, patients with COVID-19 had a clearly different phenotype and a higher mortality than non-COVID-19 patients. This may help to outline more accurate screening and appropriate and timely treatment for these patients.

RESUMO Objetivo: Comparar, em uma coorte de pacientes com insuficiência respiratória aguda, os fenótipos de pacientes com e sem COVID-19, no contexto da pandemia, e avaliar se a COVID-19 é um preditor independente de mortalidade na unidade de terapia intensiva. Métodos: Este estudo de coorte histórico avaliou 1.001 pacientes com insuficiência respiratória aguda e suspeita de COVID-19 internados na unidade de terapia intensiva de oito hospitais. Os pacientes foram classificados como casos com e sem COVID-19 segundo os resultados da RT-PCR. Foram coletados dados sobre características clínicas e demográficas na admissão à unidade de terapia intensiva, bem como dados clínicos e laboratoriais diários e desfechos da unidade de terapia intensiva. Resultados: Embora os grupos não tenham diferido nos escores APACHE II ou SOFA na admissão, o grupo COVID-19 apresentou mais sintomas iniciais de febre, mialgia e diarreia e teve maior duração dos sintomas e maior prevalência de obesidade. Eles também apresentaram menor relação PaO2/FiO2 e níveis mais baixos de plaquetas do que os pacientes sem COVID-19 e mais alterações metabólicas, como níveis mais altos de glicemia, proteína C-reativa e desidrogenase lática. Os pacientes com insuficiência respiratória aguda sem COVID-19 apresentaram maior prevalência de doença pulmonar obstrutiva crônica/asma e cardiopatia. Os pacientes com COVID-19 permaneceram mais tempo no hospital e tiveram mais complicações, como insuficiência renal aguda, síndrome do desconforto respiratório agudo grave e infecção grave. A taxa de mortalidade por todas as causas também foi maior nesse grupo (43,7% no grupo com COVID-19 versus 27,4% no grupo sem COVID-19). O diagnóstico de COVID-19 foi um preditor de mortalidade na unidade de terapia intensiva (razão de chances de 2,77; IC95% 1,89 - 4,07; p < 0,001), independentemente da idade ou da pontuação do Índice de Comorbidade de Charlson. Conclusão: Em uma coorte prospectiva de pacientes admitidos com insuficiência respiratória aguda, os pacientes com COVID-19 apresentaram fenótipo claramente diferente e uma mortalidade mais alta do que os pacientes sem COVID-19. Isso pode ajudar a traçar uma triagem mais precisa e um tratamento adequado e oportuno para esses pacientes.

Diagnostic accuracy of a set of clinical and radiological criteria for screening of COVID-19 using RT-PCR as the reference standard.

BACKGROUND: The gold-standard method for establishing a microbiological diagnosis of COVID-19 is reverse-transcriptase polymerase chain reaction (RT-PCR). This study aimed to evaluate the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a set of clinical-radiological criteria for COVID-19 screening in patients with severe acute respiratory failure (SARF) admitted to intensive care units (ICUs), using reverse-transcriptase polymerase chain reaction (RT-PCR) as the reference standard. METHODS: Diagnostic accuracy study including a historical cohort of 1009 patients consecutively admitted to ICUs across six hospitals in Curitiba (Brazil) from March to September, 2020. The sample was stratified into groups by the strength of suspicion for COVID-19 (strong versus weak) using parameters based on three clinical and radiological (chest computed tomography) criteria. The diagnosis of COVID-19 was confirmed by RT-PCR (referent). RESULTS: With respect to RT-PCR, the proposed criteria had 98.5% (95% confidence interval [95% CI] 97.5-99.5%) sensitivity, 70% (95% CI 65.8-74.2%) specificity, 85.5% (95% CI 83.4-87.7%) accuracy, PPV of 79.7% (95% CI 76.6-82.7%) and NPV of 97.6% (95% CI 95.9-99.2%). Similar performance was observed when evaluated in the subgroups of patients admitted with mild/moderate respiratory disfunction, and severe respiratory disfunction. CONCLUSION: The proposed set of clinical-radiological criteria were accurate in identifying patients with strong versus weak suspicion for COVID-19 and had high sensitivity and considerable specificity with respect to RT-PCR. These criteria may be useful for screening COVID-19 in patients presenting with SARF.

Epidemiological and clinical characteristics predictive of ICU mortality of patients with traumatic brain injury treated at a trauma referral hospital - a cohort study.

BACKGROUND: Traumatic brain injury (TBI) has substantial physical, psychological, social and economic impacts, with high rates of morbidity and mortality. Considering its high incidence, the aim of this study was to identify epidemiological and clinical characteristics that predict mortality in patients hospitalized for TBI in intensive care units (ICUs). METHODS: A retrospective cohort study was carried out with patients over 18 years old with TBI admitted to an ICU of a Brazilian trauma referral hospital between January 2012 and August 2019. TBI was compared with other traumas in terms of clinical characteristics of ICU admission and outcome. Univariate and multivariate analyses were used to estimate the odds ratio for mortality. RESULTS: Of the 4816 patients included, 1114 had TBI, with a predominance of males (85.1%). Compared with patients with other traumas, patients with TBI had a lower mean age (45.3 ± 19.1 versus 57.1 ± 24.1 years, p < 0.001), higher median APACHE II (19 versus 15, p < 0.001) and SOFA (6 versus 3, p < 0.001) scores, lower median Glasgow Coma Scale (GCS) score (10 versus 15, p < 0.001), higher median length of stay (7 days versus 4 days, p < 0.001) and higher mortality (27.6% versus 13.3%, p < 0.001). In the multivariate analysis, the predictors of mortality were older age (OR: 1.008 [1.002-1.015], p = 0.016), higher APACHE II score (OR: 1.180 [1.155-1.204], p < 0.001), lower GCS score for the first 24 h (OR: 0.730 [0.700-0.760], p < 0.001), greater number of brain injuries and presence of associated chest trauma (OR: 1.727 [1.192-2.501], p < 0.001). CONCLUSION: Patients admitted to the ICU for TBI were younger and had worse prognostic scores, longer hospital stays and higher mortality than those admitted to the ICU for other traumas. The independent predictors of mortality were older age, high APACHE II score, low GCS score, number of brain injuries and association with chest trauma.

Typical phenotypes of patients with acute respiratory failure with and without COVID-19 and their relationship with outcomes: a cohort study.

OBJECTIVE: To compare, within a cohort of patients with acute respiratory failure, the phenotypes of patients with and without COVID-19 in the context of the pandemic and evaluate whether COVID-19 is an independent predictor of intensive care unit mortality. METHODS: This historical cohort study evaluated 1001 acute respiratory failure patients with suspected COVID-19 admitted to the intensive care unit of 8 hospitals. Patients were classified as COVID-19 cases and non-COVID-19 cases according to real-time polymerase chain reaction results. Data on clinical and demographic characteristics were collected on intensive care unit admission, as well as daily clinical and laboratory data and intensive care unit outcomes. RESULTS: Although the groups did not differ in terms of APACHE II or SOFA scores at admission, the COVID-19 group had more initial symptoms of fever, myalgia and diarrhea, had a longer duration of symptoms, and had a higher prevalence of obesity. They also had a lower PaO2/FiO2 ratio, lower platelet levels than non-COVID-19 patients, and more metabolic changes, such as higher levels of blood glucose, C-reactive protein, and lactic dehydrogenase. Patients with non-COVID-19 acute respiratory failure had a higher prevalence of chronic obstructive pulmonary disease/asthma and cardiopathy. Patients with COVID-19 stayed in the hospital longer and had more complications, such as acute kidney failure, severe acute respiratory distress syndrome and severe infection. The all-cause mortality rate was also higher in this group (43.7% in the COVID-19 group versus 27.4% in the non-COVID-19 group). The diagnosis of COVID-19 was a predictor of intensive care unit mortality (odds ratio, 2.77; 95%CI, 1.89 - 4.07; p < 0.001), regardless of age or Charlson Comorbidity Index score. CONCLUSION: In a prospective cohort of patients admitted with acute respiratory failure, patients with COVID-19 had a clearly different phenotype and a higher mortality than non-COVID-19 patients. This may help to outline more accurate screening and appropriate and timely treatment for these patients.

Cohort study protocol of the Brazilian collaborative research network on COVID-19: strengthening WHO global data.

INTRODUCTION: With the COVID-19 pandemic, hospitals in low-income countries were faced with a triple challenge. First, a large number of patients required hospitalisation because of the infection's more severe symptoms. Second, there was a lack of systematic and broad testing policies for early identification of cases. Third, there were weaknesses in the integration of information systems, which led to the need to search for available information from the hospital information systems. Accordingly, it is also important to state that relevant aspects of COVID-19's natural history had not yet been fully clarified. The aim of this research protocol is to present the strategies of a Brazilian network of hospitals to perform systematised data collection on COVID-19 through the WHO platform. METHODS AND ANALYSIS: This is a multicentre project among Brazilian hospitals to provide data on COVID-19 through the WHO global platform, which integrates patient care information from different countries. From October 2020 to March 2021, a committee worked on defining a flowchart for this platform, specifying the variables of interest, data extraction standardisation and analysis. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committee (CEP) of the Research Coordinating Center of Brazil (CEP of the Hospital Nossa Senhora da Conceicao), on 29 January 2021, under approval No. 4.515.519 and by the National Research Ethics Commission (CONEP), on 5 February 2021, under approval No. 4.526.456. The project results will be explained in WHO reports and published in international peer-reviewed journals, and summaries will be provided to the funders of the study.

An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients.

Despite several studies designed to evaluate the efficacy of chloroquine and hydroxychloroquine in the treatment of coronavirus disease 2019 (COVID-19), there is still doubt about the effects of these drugs, especially in patients with severe forms of the disease. This randomized, open-label, controlled, phase III trial assessed the efficacy of chloroquine or hydroxychloroquine for five days in combination with standard care compared to standard care alone in patients hospitalized with severe COVID-19. Chloroquine 450 mg BID on day 1 and 450 mg once daily from days 2 to 5 or hydroxychloroquine 400 mg BID on day 1 and 400 mg once daily from days 2 to 5 were administered in the intervention group. Patients were enrolled from April 16 to August 06, 2020, in 6 hospitals in southern Brazil. The primary outcome was the clinical status measured on day 14 after randomization with a 9-point ordinal scale. The main secondary outcomes were all-cause mortality; invasive mechanical ventilation use; the incidence of acute renal dysfunction in 28 days; and the clinical status of patients on days 5, 7, 10 and 28. All patients with a positive RT-PCR result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were analyzed (modified intention to treat (mITT) population). Arrythmias and cardiovascular complications were assessed as safety outcomes. A total of 105 patients were enrolled and followed for 28 days. The trial was stopped before reaching the planned sample size due to harmful effects. Patients in the intervention group had a worse clinical outcome on the 14th day (odds ratio (OR) 2.45 [1.17 to 4.93], p = 0.016) and on the 28th day (OR 2.47 [1.15 to 5.30], p = 0.020). Moreover, the intervention group had higher incidences of invasive mechanical ventilation use (risk ratio (RR) 2.15 [1.05 to 4.40], p = 0.030) and severe renal dysfunction (KDIGO stage 3) (RR 2.24 [1.01 to 4.99], p = 0.042) until the 28th day of follow-up. No significant arrythmia was noted. In patients with severe COVID-19, the use of chloroquine/hydroxychloroquine added to standard treatment resulted in a significant worsening of clinical status, an increased risk of renal dysfunction and an increased need for invasive mechanical ventilation.Trial Registration: ClinicalTrials.gov, NCT04420247. Registered 09 June 2020-Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT04420247 .

Epidemiologia e desfecho dos pacientes de alto risco cirúrgico admitidos em unidades de terapia intensiva no Brasil / Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil

RESUMO Objetivo: Definir o perfil epidemiológico e os principais determinantes de morbimortalidade dos pacientes cirúrgicos não cardíacos de alto risco no Brasil. Métodos: Estudo prospectivo, observacional e multicêntrico. Todos os pacientes cirúrgicos não cardíacos admitidos nas unidades de terapia intensiva, ou seja, considerados de alto risco, no período de 1 mês, foram avaliados e acompanhados diariamente por, no máximo, 7 dias na unidade de terapia intensiva, para determinação de complicações. As taxas de mortalidade em 28 dias de pós-operatório, na unidade de terapia intensiva e hospitalar foram avaliadas. Resultados: Participaram 29 unidades de terapia intensiva onde foram realizadas cirurgias em 25.500 pacientes, dos quais 904 (3,5%) de alto risco (intervalo de confiança de 95% - IC95% 3,3% - 3,8%), tendo sido incluídos no estudo. Dos pacientes envolvidos, 48,3% eram de unidades de terapia intensiva privadas e 51,7% de públicas. O tempo de internação na unidade de terapia intensiva foi de 2,0 (1,0 - 4,0) dias e hospitalar de 9,5 (5,4 - 18,6) dias. As taxas de complicações foram 29,9% (IC95% 26,4 - 33,7) e mortalidade em 28 dias pós-cirurgia 9,6% (IC95% 7,4 - 12,1). Os fatores independentes de risco para complicações foram Simplified Acute Physiology Score 3 (SAPS 3; razão de chance − RC = 1,02; IC95% 1,01 - 1,03) e Sequential Organ Failure Assessment Score (SOFA) da admissão na unidade de terapia intensiva (RC =1,17; IC95% 1,09 - 1,25), tempo de cirurgia (RC = 1,001; IC95% 1,000 - 1,002) e cirurgias de emergências (RC = 1,93; IC95% 1,10 - 3,38). Em adição, foram associados com mortalidade em 28 dias idade (RC = 1,032; IC95% 1,011 - 1,052) SAPS 3 (RC = 1,041; IC95% 1,107 - 1,279), SOFA (RC = 1,175; IC95% 1,069 - 1,292) e cirurgias emergenciais (RC = 2,509; IC95% 1,040 - 6,051). Conclusão: Pacientes com escores prognósticos mais elevados, idosos, tempo cirúrgico e cirurgias emergenciais estiveram fortemente associados a maior mortalidade em 28 dias e mais complicações durante permanência em unidade de terapia intensiva.

ABSTRACT Objective: To define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil. Methods: This was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated. Results: Twenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051). Conclusion: Higher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.