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.

Accuracy of the persistent AKI risk index in predicting acute kidney injury in patients admitted to the intensive care unit for acute respiratory failure.

OBJECTIVE: To evaluate the accuracy of the persistent AKI risk index (PARI) in predicting acute kidney injury within 72 hours after admission to the intensive care unit, persistent acute kidney injury, renal replacement therapy, and death within 7 days in patients hospitalized due to acute respiratory failure. METHODS: This study was done in a cohort of diagnoses of consecutive adult patients admitted to the intensive care unit of eight hospitals in Curitiba, Brazil, between March and September 2020 due to acute respiratory failure secondary to suspected COVID-19. The COVID-19 diagnosis was confirmed or refuted by RT-PCR for the detection of SARS-CoV-2. The ability of PARI to predict acute kidney injury at 72 hours, persistent acute kidney injury, renal replacement therapy, and death within 7 days was analyzed by ROC curves in comparison to delta creatinine, SOFA, and APACHE II. RESULTS: Of the 1,001 patients in the cohort, 538 were included in the analysis. The mean age was 62 ± 17 years, 54.8% were men, and the median APACHE II score was 12. At admission, the median SOFA score was 3, and 83.3% had no renal dysfunction. After admission to the intensive care unit, 17.1% had acute kidney injury within 72 hours, and through 7 days, 19.5% had persistent acute kidney injury, 5% underwent renal replacement therapy, and 17.1% died. The PARI had an area under the ROC curve of 0.75 (0.696 - 0.807) for the prediction of acute kidney injury at 72 hours, 0.71 (0.613 - 0.807) for renal replacement therapy, and 0.64 (0.565 - 0.710) for death. CONCLUSION: The PARI has acceptable accuracy in predicting acute kidney injury within 72 hours and renal replacement therapy within 7 days of admission to the intensive care unit, but it is not significantly better than the other scores.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study.

BACKGROUND: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. METHODS: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. CONCLUSION: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. CLINICALTRIALS.GOV REGISTRY: NCT05558098.

Long-term Health-Related Quality of Life and Outcomes after Hospitalization for COVID-19 in Brazil: Post-COVID Brazil 1 Study Protocol. / Qualidade de Vida em Longo Prazo e Desfechos após Internação por COVID-19 no Brasil: Protocolo do Estudo Pós-COVID Brasil 1.

BACKGROUND: The long-term impact of hospitalization for COVID-19 on patients' physical, mental, and cognitive health still needs further assessment. OBJECTIVES: This study aims to evaluate factors associated with quality of life and cardiovascular and non-cardiovascular outcomes 12 months after hospitalization for COVID-19. METHODS: This prospective multicenter study intends to enroll 611 patients hospitalized due to COVID-19 (NCT05165979). Centralized telephone interviews are scheduled to occur at three, six, nine, and 12 months after hospital discharge. The primary endpoint is defined as the health-related quality-of-life utility score assessed by the EuroQol-5D-3L (EQ-5D-3L) questionnaire at 12 months. Secondary endpoints are defined as the EQ-5D-3L at three, six and nine months, return to work or education, persistent symptoms, new disabilities in instrumental activities of daily living, cognitive impairment, anxiety, depression, and post-traumatic stress symptoms, major cardiovascular events, rehospitalization, as well as all-cause mortality at 3, 6, 9, and 12 months after SARS-CoV-2 infection. A p-value <0.05 will be assumed as statistically significant for all analyses. RESULTS: The primary endpoint will be presented as the frequency of the EQ-5D-3L score 12 months after COVID-19 hospitalization. A sub-analysis to identify possible associations of independent variables with study outcomes will be presented. CONCLUSIONS: This study will determine the impact of COVID-19 on the quality of life and cardiovascular and non-cardiovascular outcomes of hospitalized patients 12 months after discharge providing insights to the public health system in Brazil.

FUNDAMENTO: O impacto em longo prazo da hospitalização por COVID-19 sobre a saúde física, mental e cognitiva dos pacientes requer mais investigação. OBJETIVOS: Este artigo visa avaliar os fatores associados com a qualidade de vida e desfechos cardiovasculares e não cardiovasculares 12 meses após a internação hospitalar por COVID-19. MÉTODOS: Este estudo multicêntrico prospectivo pretende incluir 611 pacientes internados por COVID-19 (NCT05165979). Entrevistas telefônicas centralizadas estão programadas para ocorrer em três, seis, nove e 12 meses após a alta hospitalar. O desfecho primário é definido como o escore de utilidade de qualidade de vida relacionada à saúde avaliada pelo questionário EuroQol-5D-3L (EQ-5D-3L) aos 12 meses. Desfechos secundários são definidos como o EQ-5D-3L aos três, seis e nove meses, retorno ao trabalho ou à escola, sintomas persistentes, novas incapacidades em atividades instrumentais diárias, déficit cognitivo, ansiedade, depressão, e sintomas de transtorno do estresse pós-traumático, eventos cardiovasculares maiores, reinternação, e mortalidade por todas as causas aos três, seis, nove e 12 meses após a infecção pelo SARS-CoV-2. Um valor de p<0,05 será considerado estatisticamente significativo para as análises. RESULTADOS: O desfecho primário será apresentado como frequência do escore EQ-5D-3L 12 meses após a internação por COVID-19. Uma subanálise para identificar possíveis associações das variáveis independentes com desfechos do estudo será apresentada. CONCLUSÃO: Este estudo determinará o impacto da COVID-19 sobre a qualidade de vida e de desfechos cardiovasculares e não cardiovasculares de pacientes internados 12 meses após a alta, e fornecerá novas informações ao sistema público de saúde no Brasil.

Health-Related Quality of Life and Long-Term Outcomes after Mildly Symptomatic COVID-19: The Post-COVID Brazil Study 2 Protocol. / Qualidade de Vida Relacionada à Saúde e Desfechos em Longo Prazo após COVID-19 Sintomática Leve: Protocolo do Estudo Pós-COVID Brasil 2.

BACKGROUND: The long-term effects of mild COVID-19 on physical, cognitive, and mental health are not yet well understood. OBJECTIVE: The purpose of this paper is to describe the protocol for the ongoing "Post-COVID Brazil" study 2, which aims to evaluate the factors associated with health-related quality of life and long-term cardiovascular and non-cardiovascular outcomes one year after a mild episode of symptomatic COVID-19. METHODS: The "Post-COVID Brazil" study 2 is a prospective multicenter study that plans to enroll 1047 patients (NCT05197647). Centralized, structured telephone interviews are conducted at 1, 3, 6, 9, and 12 months after COVID-19 diagnosis. The primary outcome is the health-related quality-of-life utility score, assessed using the EuroQol-5D-3L (EQ-5D-3L) questionnaire at 12 months. Secondary endpoints include the EQ-5D-3L at 3, 6, and 9 months, as well as all-cause mortality, major cardiovascular events, hospitalization, return to work or education, persistent symptoms, new disabilities in instrumental activities of daily living, cognitive impairment, anxiety, depression, and post-traumatic stress symptoms at 3, 6, 9, and 12 months after SARS-CoV-2 infection. A p-value < 0.05 will be considered statistically significant for all analyses. RESULTS: The primary endpoint will be presented as the overall frequency of the EQ-5D-3L domains 12 months after SARS-CoV-2 infection. Main analysis will explore the association of independent variables with the study outcomes. CONCLUSION: The "Post-COVID Brazil" study 2 aims to clarify the impact of long COVID on the quality of life and cardiovascular and non-cardiovascular outcomes of Brazilian patients who have had mild COVID-19.

FUNDAMENTO: Os efeitos em longo prazo da COVID-19 leve sobre a saúde física, mental e cognitiva ainda não são bem conhecidos. OBJETIVO: Este artigo visa descrever o protocolo para o estudo em andamento Pós-COVID Brasil 2, o qual tem como objetivo avaliar os fatores associados à qualidade de vida associada à saúde e desfechos cardiovasculares e não cardiovasculares de longo prazo um ano após um episódio de COVID-19 sintomática leve. MÉTODOS: O estudo "Pós-COVID Brasil 2" é um estudo multicêntrico prospectivo que pretende incluir 1047 pacientes (NCT05197647). Entrevistas estruturas, centralizadas são conduzidas em um mês, e aos três, seis, nove e 12 meses após o diagnóstico de COVID-19. O desfecho primário é o escore de utilidade da qualidade de vida relacionada à saúde, avaliado usando o questionário EuroQol-5D-3L (EQ-5D-3L) aos 12 meses. Desfechos secundários incluem o EQ-5D-3L aos três, seis e nove meses, mortalidade por todas as causas, eventos cardiovasculares maiores, hospitalização, retorno ao trabalho ou à escola, sintomas persistentes, novas incapacidades em atividades instrumentais diárias, déficit cognitivo, ansiedade, depressão, e sintomas de transtorno do estresse pós-traumático as três, seis, nove e doze meses após a infecção pelo SARS-CoV-2. Um valor de p<0,05 será considerado estatisticamente significativo para as análises. RESULTADOS: O desfecho primário será apresentado como frequência dos domínios do EQ-5D-3L doze meses após a infecção por SARS-CoV-2. A análise principal explorará a associação das variáveis independentes com os desfechos do estudo. CONCLUSÃO: O estudo "Pós-COVID Brasil 2" tem como objetivo elucidar o impacto da COVID longa sobre a qualidade de vida e desfechos cardiovasculares e não cardiovasculares de brasileiros pacientes que apresentaram COVID-19 leve.

Epidemiology and disease burden of patients requiring neurocritical care: a Brazilian multicentre cohort study.

Acute neurological emergencies are highly prevalent in intensive care units (ICUs) and impose a substantial burden on patients. This study aims to describe the epidemiology of patients requiring neurocritical care in Brazil, and their differences based on primary acute neurological diagnoses and to identify predictors of mortality and unfavourable outcomes, along with the disease burden of each condition at intensive care unit admission. This prospective cohort study included patients requiring neurocritical care admitted to 36 ICUs in four Brazilian regions who were followed for 30 days or until ICU discharge (Aug-Sep in 2018, 1 month). Of 4245 patients admitted to the participating ICUs, 1194 (28.1%) were patients with acute neurological disorders requiring neurocritical care and were included. Patients requiring neurocritical care had a mean mortality rate 1.7 times higher than ICU patients not requiring neurocritical care (17.21% versus 10.1%, respectively). Older age, emergency admission, higher number of potential secondary injuries, and worse APACHE II, SAPS III, SOFA, and Glasgow coma scale scores on ICU admission are independent predictors of mortality and poor outcome among patients with acute neurological diagnoses. The estimated total DALYs were 4482.94 in the overall cohort, and the diagnosis with the highest DALYs was traumatic brain injury (1634.42). Clinical, epidemiological, treatment, and ICU outcome characteristics vary according to the primary neurologic diagnosis. Advanced age, a lower GCS score and a higher number of potential secondary injuries are independent predictors of mortality and unfavourable outcomes in patients requiring neurocritical care. The findings of this study are essential to guide education policies, prevention, and treatment of severe acute neurocritical diseases.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study / Dapagliflozina em pacientes com doença crítica: justificativa e desenho do estudo DEFENDER

ABSTRACT Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry: NCT05558098

RESUMO Antecedentes: A doença crítica é um importante ônus permanente da assistência médica em todo o mundo e está associada a altas taxas de mortalidade. Os inibidores do cotransportador de sódio-glicose do tipo 2 têm demonstrado consistentemente benefícios nos desfechos cardiovasculares e renais. Os efeitos dos inibidores do cotransportador de sódio-glicose do tipo 2 em doenças agudas ainda não foram devidamente investigados. Métodos: O DEFENDER é um estudo de iniciativa do investigador, multicêntrico, randomizado, aberto, desenhado para avaliar a eficácia e a segurança da dapagliflozina em 500 participantes adultos com disfunção orgânica aguda hospitalizados na unidade de terapia intensiva. Os participantes aptos serão randomizados 1:1 para receber 10mg de dapagliflozina e o tratamento padrão por até 14 dias ou apenas o tratamento padrão. O desfecho primário é um composto hierárquico de mortalidade hospitalar, início de terapia renal substitutiva e tempo de internação na unidade de terapia intensiva, até 28 dias. O monitoramento da segurança será rigoroso durante todo o estudo. Conclusão: O DEFENDER é o primeiro estudo desenvolvido para investigar o uso de um inibidor do cotransportador de sódio-glicose do tipo 2 em pacientes de unidade de terapia intensiva geral com disfunção orgânica aguda. O estudo fornecerá informações relevantes sobre o uso de medicamentos dessa classe promissora em pacientes críticos. Registro ClincalTrials.gov: NCT05558098

Accuracy of the persistent AKI risk index in predicting acute kidney injury in patients admitted to the intensive care unit for acute respiratory failure / Acurácia do persistent AKI risk index na predição de injúria renal aguda em pacientes admitidos na unidade de terapia intensiva por insuficiência respiratória aguda

ABSTRACT Objective: To evaluate the accuracy of the persistent AKI risk index (PARI) in predicting acute kidney injury within 72 hours after admission to the intensive care unit, persistent acute kidney injury, renal replacement therapy, and death within 7 days in patients hospitalized due to acute respiratory failure. Methods: This study was done in a cohort of diagnoses of consecutive adult patients admitted to the intensive care unit of eight hospitals in Curitiba, Brazil, between March and September 2020 due to acute respiratory failure secondary to suspected COVID-19. The COVID-19 diagnosis was confirmed or refuted by RT-PCR for the detection of SARS-CoV-2. The ability of PARI to predict acute kidney injury at 72 hours, persistent acute kidney injury, renal replacement therapy, and death within 7 days was analyzed by ROC curves in comparison to delta creatinine, SOFA, and APACHE II. Results: Of the 1,001 patients in the cohort, 538 were included in the analysis. The mean age was 62 ± 17 years, 54.8% were men, and the median APACHE II score was 12. At admission, the median SOFA score was 3, and 83.3% had no renal dysfunction. After admission to the intensive care unit, 17.1% had acute kidney injury within 72 hours, and through 7 days, 19.5% had persistent acute kidney injury, 5% underwent renal replacement therapy, and 17.1% died. The PARI had an area under the ROC curve of 0.75 (0.696 - 0.807) for the prediction of acute kidney injury at 72 hours, 0.71 (0.613 - 0.807) for renal replacement therapy, and 0.64 (0.565 - 0.710) for death. Conclusion: The PARI has acceptable accuracy in predicting acute kidney injury within 72 hours and renal replacement therapy within 7 days of admission to the intensive care unit, but it is not significantly better than the other scores.

RESUMO Objetivo: Avaliar a acurácia do persistent AKI risk index (PARI) na predição de injúria renal aguda em 72 horas após a admissão em unidade de terapia intensiva, injúria renal aguda persistente, terapia de substituição renal e óbito, em até 7 dias em pacientes internados por insuficiência respiratória aguda. Métodos: Estudo de método-diagnóstico com base em coorte de inclusão consecutiva de pacientes adultos internados em unidade de terapia intensiva de oito hospitais de Curitiba (PR) entre março e setembro de 2020, por insuficiência respiratória aguda secundária à suspeita de COVID-19, com confirmação ou refutação diagnóstica dada pelo resultado de RT-PCR para detecção do SARS-CoV-2. O potencial preditor do PARI foi analisado por curva ROC em relação a delta creatinina, SOFA e APACHE II, para os desfechos injúria renal aguda em 72 horas; injúria renal aguda persistente; terapia de substituição renal e mortalidade em até 7 dias. Resultados: Dos 1.001 pacientes da coorte, 538 foram incluídos na análise. A média de idade foi de 62 ± 17 anos, 54,8% eram homens e o APACHE II mediano foi de 12. Na admissão, o SOFA mediano era 3, e 83,3% não apresentavam disfunção renal. Após admissão na unidade de terapia intensiva, 17,1% apresentaram injúria renal aguda em 72 horas e, até o sétimo dia, 19,5% apresentaram injúria renal aguda persistente, 5% realizaram terapia de substituição renal, e 17,1% foram a óbito. O PARI apresentou área sob a curva ROC de 0,75 (0,696 - 0,807) para predição de injúria renal aguda em 72 horas, 0,71 (0,613 - 0,807) para terapia de substituição renal e 0,64 (0,565 - 0,710) para mortalidade. Conclusão: O PARI tem acurácia aceitável na predição de injúria renal aguda em 72 horas e terapia de substituição renal em até 7 dias da admissão na unidade de terapia intensiva, porém sem diferença significativa dos demais escores.

Dysglycemias in patients admitted to ICUs with severe acute respiratory syndrome due to COVID-19 versus other causes - a cohort study.

BACKGROUND: Dysglycemias have been associated with worse prognosis in critically ill patients with COVID-19, but data on the association of dysglycemia with COVID-19 in comparison with other forms of severe acute respiratory syndrome are lacking. This study aimed to compare the occurrence of different glycemic abnormalities in patients with severe acute respiratory syndrome and COVID-19 admitted to intensive care units versus glycemic abnormalities in patients with severe acute respiratory syndrome from other causes, to evaluate the adjusted attributable risk associated with COVID-19 and dysglycemia and to assess the influence of these dysglycemias on mortality. METHODS: We conducted a retrospective cohort of consecutive patients with severe acute respiratory syndrome and suspected COVID-19 hospitalized in intensive care units between March 11 and September 13, 2020, across eight hospitals in Curitiba-Brazil. The primary outcome was the influence of COVID-19 on the variation of the following parameters of dysglycemia: highest glucose level at admission, mean and highest glucose levels during ICU stay, mean glucose variability, percentage of days with hyperglycemia, and hypoglycemia during ICU stay. The secondary outcome was the influence of COVID-19 and each of the six parameters of dysglycemia on hospital mortality within 30 days from ICU admission. RESULTS: The sample consisted of 841 patients, of whom 703 with and 138 without COVID-19. Comparing patients with and without COVID-19, those with COVID-19 had significantly higher glucose peaks at admission (165 mg/dL vs. 146 mg/dL; p = 0.002) and during ICU stay (242 mg/dL vs. 187md/dL; p < 0.001); higher mean daily glucose (149.7 mg/dL vs. 132.6 mg/dL; p < 0.001); higher percentage of days with hyperglycemia during ICU stay (42.9% vs. 11.1%; p < 0.001); and greater mean glucose variability (28.1 mg/dL vs. 25.0 mg/dL; p = 0.013). However, these associations were no longer statistically significant after adjustment for Acute Physiology and Chronic Health Evaluation II scores, Sequential Organ Failure Assessment scores, and C-reactive protein level, corticosteroid use and nosocomial infection. Dysglycemia and COVID-19 were each independent risk factors for mortality. The occurrence of hypoglycemia (< 70 mg/dL) during ICU stay was not associated with COVID-19. CONCLUSION: Patients with severe acute respiratory syndrome due to COVID-19 had higher mortality and more frequent dysglycemia than patients with severe acute respiratory syndrome due to other causes. However, this association did not seem to be directly related to the SARS-CoV-2 infection.

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.

Qualidade de Vida em Longo Prazo e Desfechos após Internação por COVID-19 no Brasil: Protocolo do Estudo Pós-COVID Brasil 1 / Long-term Health-Related Quality of Life and Outcomes after Hospitalization for COVID-19 in Brazil: Post-COVID Brazil 1 Study Protocol

Resumo Fundamento O impacto em longo prazo da hospitalização por COVID-19 sobre a saúde física, mental e cognitiva dos pacientes requer mais investigação. Objetivos Este artigo visa avaliar os fatores associados com a qualidade de vida e desfechos cardiovasculares e não cardiovasculares 12 meses após a internação hospitalar por COVID-19. Métodos Este estudo multicêntrico prospectivo pretende incluir 611 pacientes internados por COVID-19 (NCT05165979). Entrevistas telefônicas centralizadas estão programadas para ocorrer em três, seis, nove e 12 meses após a alta hospitalar. O desfecho primário é definido como o escore de utilidade de qualidade de vida relacionada à saúde avaliada pelo questionário EuroQol-5D-3L (EQ-5D-3L) aos 12 meses. Desfechos secundários são definidos como o EQ-5D-3L aos três, seis e nove meses, retorno ao trabalho ou à escola, sintomas persistentes, novas incapacidades em atividades instrumentais diárias, déficit cognitivo, ansiedade, depressão, e sintomas de transtorno do estresse pós-traumático, eventos cardiovasculares maiores, reinternação, e mortalidade por todas as causas aos três, seis, nove e 12 meses após a infecção pelo SARS-CoV-2. Um valor de p<0,05 será considerado estatisticamente significativo para as análises. Resultados O desfecho primário será apresentado como frequência do escore EQ-5D-3L 12 meses após a internação por COVID-19. Uma subanálise para identificar possíveis associações das variáveis independentes com desfechos do estudo será apresentada. Conclusão Este estudo determinará o impacto da COVID-19 sobre a qualidade de vida e de desfechos cardiovasculares e não cardiovasculares de pacientes internados 12 meses após a alta, e fornecerá novas informações ao sistema público de saúde no Brasil.

Abstract Background The long-term impact of hospitalization for COVID-19 on patients' physical, mental, and cognitive health still needs further assessment. Objectives This study aims to evaluate factors associated with quality of life and cardiovascular and non-cardiovascular outcomes 12 months after hospitalization for COVID-19. Methods This prospective multicenter study intends to enroll 611 patients hospitalized due to COVID-19 (NCT05165979). Centralized telephone interviews are scheduled to occur at three, six, nine, and 12 months after hospital discharge. The primary endpoint is defined as the health-related quality-of-life utility score assessed by the EuroQol-5D-3L (EQ-5D-3L) questionnaire at 12 months. Secondary endpoints are defined as the EQ-5D-3L at three, six and nine months, return to work or education, persistent symptoms, new disabilities in instrumental activities of daily living, cognitive impairment, anxiety, depression, and post-traumatic stress symptoms, major cardiovascular events, rehospitalization, as well as all-cause mortality at 3, 6, 9, and 12 months after SARS-CoV-2 infection. A p-value <0.05 will be assumed as statistically significant for all analyses. Results The primary endpoint will be presented as the frequency of the EQ-5D-3L score 12 months after COVID-19 hospitalization. A sub-analysis to identify possible associations of independent variables with study outcomes will be presented. Conclusions This study will determine the impact of COVID-19 on the quality of life and cardiovascular and non-cardiovascular outcomes of hospitalized patients 12 months after discharge providing insights to the public health system in Brazil.

Qualidade de Vida Relacionada à Saúde e Desfechos em Longo Prazo após COVID-19 Sintomática Leve: Protocolo do Estudo Pós-COVID Brasil 2 / Health-Related Quality of Life and Long-Term Outcomes after Mildly Symptomatic COVID-19: The Post-COVID Brazil Study 2 Protocol

Resumo Fundamento Os efeitos em longo prazo da COVID-19 leve sobre a saúde física, mental e cognitiva ainda não são bem conhecidos. Objetivo Este artigo visa descrever o protocolo para o estudo em andamento Pós-COVID Brasil 2, o qual tem como objetivo avaliar os fatores associados à qualidade de vida associada à saúde e desfechos cardiovasculares e não cardiovasculares de longo prazo um ano após um episódio de COVID-19 sintomática leve. Métodos O estudo "Pós-COVID Brasil 2" é um estudo multicêntrico prospectivo que pretende incluir 1047 pacientes (NCT05197647). Entrevistas estruturas, centralizadas são conduzidas em um mês, e aos três, seis, nove e 12 meses após o diagnóstico de COVID-19. O desfecho primário é o escore de utilidade da qualidade de vida relacionada à saúde, avaliado usando o questionário EuroQol-5D-3L (EQ-5D-3L) aos 12 meses. Desfechos secundários incluem o EQ-5D-3L aos três, seis e nove meses, mortalidade por todas as causas, eventos cardiovasculares maiores, hospitalização, retorno ao trabalho ou à escola, sintomas persistentes, novas incapacidades em atividades instrumentais diárias, déficit cognitivo, ansiedade, depressão, e sintomas de transtorno do estresse pós-traumático as três, seis, nove e doze meses após a infecção pelo SARS-CoV-2. Um valor de p<0,05 será considerado estatisticamente significativo para as análises. Resultados O desfecho primário será apresentado como frequência dos domínios do EQ-5D-3L doze meses após a infecção por SARS-CoV-2. A análise principal explorará a associação das variáveis independentes com os desfechos do estudo. Conclusão O estudo "Pós-COVID Brasil 2" tem como objetivo elucidar o impacto da COVID longa sobre a qualidade de vida e desfechos cardiovasculares e não cardiovasculares de brasileiros pacientes que apresentaram COVID-19 leve.

Abstract Background The long-term effects of mild COVID-19 on physical, cognitive, and mental health are not yet well understood. Objective The purpose of this paper is to describe the protocol for the ongoing "Post-COVID Brazil" study 2, which aims to evaluate the factors associated with health-related quality of life and long-term cardiovascular and non-cardiovascular outcomes one year after a mild episode of symptomatic COVID-19. Methods The "Post-COVID Brazil" study 2 is a prospective multicenter study that plans to enroll 1047 patients (NCT05197647). Centralized, structured telephone interviews are conducted at 1, 3, 6, 9, and 12 months after COVID-19 diagnosis. The primary outcome is the health-related quality-of-life utility score, assessed using the EuroQol-5D-3L (EQ-5D-3L) questionnaire at 12 months. Secondary endpoints include the EQ-5D-3L at 3, 6, and 9 months, as well as all-cause mortality, major cardiovascular events, hospitalization, return to work or education, persistent symptoms, new disabilities in instrumental activities of daily living, cognitive impairment, anxiety, depression, and post-traumatic stress symptoms at 3, 6, 9, and 12 months after SARS-CoV-2 infection. A p-value < 0.05 will be considered statistically significant for all analyses. Results The primary endpoint will be presented as the overall frequency of the EQ-5D-3L domains 12 months after SARS-CoV-2 infection. Main analysis will explore the association of independent variables with the study outcomes. Conclusion The "Post-COVID Brazil" study 2 aims to clarify the impact of long COVID on the quality of life and cardiovascular and non-cardiovascular outcomes of Brazilian patients who have had mild COVID-19.

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.