Favipiravir Efficacy And Safety For The Treatment Of Severe Coronavirus Disease 2019: A Retrospective Study.

BACKGROUND: Corona virus disease is caused by the enveloped, single stranded RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becoming the deadliest disease of the century. Its global outbreak has led researchers to develop drugs or vaccines to prevent the spread of the disease. Favipiravir is an approved orally administered antiviral drug that selectively inhibits RNA-dependent RNA polymerase, used off-label to treat COVID-19. Objectives: The purpose of this study was to assess the efficacy and safety of this drug for severe COVID-19 infection. METHODS: This was an observational retrospective study, carried out at the ICU of King Saud Medical City (KSMC) from June 2020 to August 2020. Including a total of one thousand six hundred and ninety-nine patients (n=1699). Categorized into a treatment group (193 patients) who received Favipiravir along with standard care, and non-treatment group (1506 patients) who received standard care only. RESULTS: ICU all-cause mortality was similar in both groups i.e., (Treated group 38.3% Vs Untreated group 39.4%, 95% CI of difference: -6.6% to +8.4%; p = 0.8). The subgroup analysis of survivors as compared to deceased in the treatment group showed that survivors had significantly lower age, international normalising ratio (INR), blood urea nitrogen (BUN), and creatinine. The mean ICU length of stay (LOS) was shorter for survivors compared to deceased (11.2± 8.03 Vs 16.7±9.8 days respectively), while hospital LOS was almost similar between the two groups. Advanced age (OR 1.03 [95% CI: 1.01-1.06]; p=0.004), higher INR and BUN were significantly associated with increased odds of mortality. Comparison of lab investigations at day 1 and day 10 in the treatment group (regardless of outcome) showed that there was a significant increase in Alanine transaminase (ALT), alkaline phosphatase (ALK), and Bilirubin, while an insignificant trend of increase in Aspartate transaminase (AST) and creatinine was recorded. CONCLUSIONS: In this study, Favipiravir showed better therapeutic responses in patients with severe COVID-19 infection, in terms of average duration of stay in the intensive care unit and was well tolerated in the younger age, but showed no mortality benefit. However, elevated levels of inflammatory markers, including increased ALT, AST, BUN, bilirubin, and creatinine, needs to be carefully examined.

Delayed intensive care unit admission from the emergency department: impact on patient outcomes. A retrospective study. / Retardo na transferência do pronto-socorro para a unidade de terapia intensiva: impacto nos desfechos do paciente. Um estudo retrospectivo.

OBJECTIVE: To study the impact of delayed admission by more than 4 hours on the outcomes of critically ill patients. METHODS: This was a retrospective observational study in which adult patients admitted directly from the emergency department to the intensive care unit were divided into two groups: Timely Admission if they were admitted within 4 hours and Delayed Admission if admission was delayed for more than 4 hours. Intensive care unit length of stay and hospital/intensive care unit mortality were compared between the groups. Propensity score matching was performed to correct for imbalances. Logistic regression analysis was used to explore delayed admission as an independent risk factor for intensive care unit mortality. RESULTS: During the study period, 1,887 patients were admitted directly from the emergency department to the intensive care unit, with 42% being delayed admissions. Delayed patients had significantly longer intensive care unit lengths of stay and higher intensive care unit and hospital mortality. These results were persistent after propensity score matching of the groups. Delayed admission was an independent risk factor for intensive care unit mortality (OR = 2.6; 95%CI 1.9 - 3.5; p < 0.001). The association of delay and intensive care unit mortality emerged after a delay of 2 hours and was highest after a delay of 4 hours. CONCLUSION: Delayed admission to the intensive care unit from the emergency department is an independent risk factor for intensive care unit mortality, with the strongest association being after a delay of 4 hours.

OBJETIVO: Estudar o impacto do retardo na admissão à unidade de terapia intensiva em mais do que 4 horas nos desfechos de pacientes críticos. MÉTODOS: Este foi um estudo observacional retrospectivo, no qual pacientes adultos admitidos diretamente do pronto-socorro para a unidade de terapia intensiva foram divididos em dois grupos: Tempo Adequado, se admitidos dentro de 4 horas, e Admissão Retardada, nos casos em que a admissão demorou mais do que 4 horas para ocorrer. Compararam-se, entre os grupos, o tempo de permanência na unidade de terapia intensiva e a taxa de mortalidade na unidade de terapia intensiva e no hospital. Foi realizado pareamento por escore de propensão para correção de desequilíbrios. Utilizou-se uma análise de regressão logística para explorar retardo da admissão como fator independente de risco para mortalidade na unidade de terapia intensiva. RESULTADOS: Durante o período do estudo, 1.887 pacientes foram admitidos diretamente do pronto-socorro para a unidade de terapia intensiva, sendo que 42% dessas admissões foram retardadas. Os pacientes com retardo tiveram permanências na unidade de terapia intensiva significantemente mais longas e maior mortalidade na unidade de terapia intensiva e no hospital. Esses resultados persistiram após pareamento dos grupos por escore de propensão. O retardo da admissão foi fator independente de risco para mortalidade na unidade de terapia intensiva (RC = 2,6; IC95% 1,9 - 3,5; p < 0,001). A associação de retardo e mortalidade na unidade de terapia intensiva surgiu após período de retardo de 2 horas e foi mais alta após período de retardo de 4 horas. CONCLUSÃO: O retardo da admissão do pronto-socorro para a unidade de terapia intensiva é fator de risco independente para mortalidade na unidade de terapia intensiva, sendo a associação mais forte após retardo de 4 horas.

Retardo na transferência do pronto-socorro para a unidade de terapia intensiva: impacto nos desfechos do paciente. Um estudo retrospectivo / Delayed intensive care unit admission from the emergency department: impact on patient outcomes. A retrospective study

RESUMO Objetivo: Estudar o impacto do retardo na admissão à unidade de terapia intensiva em mais do que 4 horas nos desfechos de pacientes críticos. Métodos: Este foi um estudo observacional retrospectivo, no qual pacientes adultos admitidos diretamente do pronto-socorro para a unidade de terapia intensiva foram divididos em dois grupos: Tempo Adequado, se admitidos dentro de 4 horas, e Admissão Retardada, nos casos em que a admissão demorou mais do que 4 horas para ocorrer. Compararam-se, entre os grupos, o tempo de permanência na unidade de terapia intensiva e a taxa de mortalidade na unidade de terapia intensiva e no hospital. Foi realizado pareamento por escore de propensão para correção de desequilíbrios. Utilizou-se uma análise de regressão logística para explorar retardo da admissão como fator independente de risco para mortalidade na unidade de terapia intensiva. Resultados: Durante o período do estudo, 1.887 pacientes foram admitidos diretamente do pronto-socorro para a unidade de terapia intensiva, sendo que 42% dessas admissões foram retardadas. Os pacientes com retardo tiveram permanências na unidade de terapia intensiva significantemente mais longas e maior mortalidade na unidade de terapia intensiva e no hospital. Esses resultados persistiram após pareamento dos grupos por escore de propensão. O retardo da admissão foi fator independente de risco para mortalidade na unidade de terapia intensiva (RC = 2,6; IC95% 1,9 - 3,5; p < 0,001). A associação de retardo e mortalidade na unidade de terapia intensiva surgiu após período de retardo de 2 horas e foi mais alta após período de retardo de 4 horas. Conclusão: O retardo da admissão do pronto-socorro para a unidade de terapia intensiva é fator de risco independente para mortalidade na unidade de terapia intensiva, sendo a associação mais forte após retardo de 4 horas.

Abstract Objective: To study the impact of delayed admission by more than 4 hours on the outcomes of critically ill patients. Methods: This was a retrospective observational study in which adult patients admitted directly from the emergency department to the intensive care unit were divided into two groups: Timely Admission if they were admitted within 4 hours and Delayed Admission if admission was delayed for more than 4 hours. Intensive care unit length of stay and hospital/intensive care unit mortality were compared between the groups. Propensity score matching was performed to correct for imbalances. Logistic regression analysis was used to explore delayed admission as an independent risk factor for intensive care unit mortality. Results: During the study period, 1,887 patients were admitted directly from the emergency department to the intensive care unit, with 42% being delayed admissions. Delayed patients had significantly longer intensive care unit lengths of stay and higher intensive care unit and hospital mortality. These results were persistent after propensity score matching of the groups. Delayed admission was an independent risk factor for intensive care unit mortality (OR = 2.6; 95%CI 1.9 - 3.5; p < 0.001). The association of delay and intensive care unit mortality emerged after a delay of 2 hours and was highest after a delay of 4 hours. Conclusion: Delayed admission to the intensive care unit from the emergency department is an independent risk factor for intensive care unit mortality, with the strongest association being after a delay of 4 hours.

Residual Lung Injury in Patients Recovering From COVID-19 Critical Illness: A Prospective Longitudinal Point-of-Care Lung Ultrasound Study.

Scarce data exist regarding the natural history of lung lesions detected on ultrasound in those who survive severe COVID-19 pneumonia. OBJECTIVE: We performed a prospective analysis of point-of-care ultrasound (POCUS) findings in critically ill COVID-19 patients during and after hospitalization. METHODS: We enrolled 171 COVID-19 intensive care unit patients. POCUS of the lungs was performed with phased array (2-4 MHz), convex (2-6 MHz) and linear (10-15 MHz) transducers, scanning 12 lung areas. Chest computed tomography angiography was performed to exclude suspected pulmonary embolism. Survivors were clinically and sonographically evaluated during a 4 month period for evidence of residual lung injury. Chest computed tomography angiography and echocardiography were used to exclude pulmonary hypertension (PH) and chest high-resolution-computed-tomography to exclude interstitial lung disease (ILD) in symptomatic survivors. RESULTS: Cox regression analysis showed that lymphocytopenia (hazard ratio [HR]: 0.88, 95% confidence intervals [CI]: 0.68-0.96, p = .048), increased lactate (HR: 1.17, 95% CI: 0.94-1.46, p = 0.049), and D-dimers (HR: 1.21, 95% CI: 1.03-1.44, p = .03) were mortality predictors. Non-survivors had increased incidence of pulmonary abnormalities (B-lines, pleural line irregularities, and consolidations) compared to survivors (p < .05). During follow-up, POCUS with clinical and laboratory parameters integrated in the semi-quantitative Riyadh-Residual-Lung-Injury scale had sensitivity of 0.82 (95% CI: 0.76-0.89) and specificity of 0.91 (95% CI: 0.94-0.95) in predicting ILD. The prevalence of PH and ILD (non-specific-interstitial-pneumonia) was 7% and 11.8%, respectively. CONCLUSION: POCUS showed ability to monitor the evolution of severe COVID-19 pneumonia after hospital discharge, supporting its integration in clinical predictive models of residual lung injury.

Prospective Longitudinal Evaluation of Point-of-Care Lung Ultrasound in Critically Ill Patients With Severe COVID-19 Pneumonia.

OBJECTIVES: To perform a prospective longitudinal analysis of lung ultrasound findings in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Eighty-nine intensive care unit (ICU) patients with confirmed COVID-19 were prospectively enrolled and tracked. Point-of-care ultrasound (POCUS) examinations were performed with phased array, convex, and linear transducers using portable machines. The thorax was scanned in 12 lung areas: anterior, lateral, and posterior (superior/inferior) bilaterally. Lower limbs were scanned for deep venous thrombosis and chest computed tomographic angiography was performed to exclude suspected pulmonary embolism (PE). Follow-up POCUS was performed weekly and before hospital discharge. RESULTS: Patients were predominantly male (84.2%), with a median age of 43 years. The median duration of mechanical ventilation was 17 (interquartile range, 10-22) days; the ICU length of stay was 22 (interquartile range, 20.2-25.2) days; and the 28-day mortality rate was 28.1%. On ICU admission, POCUS detected bilateral irregular pleural lines (78.6%) with accompanying confluent and separate B-lines (100%), variable consolidations (61.7%), and pleural and cardiac effusions (22.4% and 13.4%, respectively). These findings appeared to signify a late stage of COVID-19 pneumonia. Deep venous thrombosis was identified in 16.8% of patients, whereas chest computed tomographic angiography confirmed PE in 24.7% of patients. Five to six weeks after ICU admission, follow-up POCUS examinations detected significantly lower rates (P < .05) of lung abnormalities in survivors. CONCLUSIONS: Point-of-care ultrasound depicted B-lines, pleural line irregularities, and variable consolidations. Lung ultrasound findings were significantly decreased by ICU discharge, suggesting persistent but slow resolution of at least some COVID-19 lung lesions. Although POCUS identified deep venous thrombosis in less than 20% of patients at the bedside, nearly one-fourth of all patients were found to have computed tomography-proven PE.

Tocilizumab in the treatment of rapidly evolving COVID-19 pneumonia and multifaceted critical illness: A retrospective case series.

BACKGROUND: COVID-19 associated critical illness characterized by rapidly evolving acute respiratory failure (ARF) can develop, especially on the grounds of hyperinflammation. AIM AND METHODS: A case-series of 61 patients admitted to our intensive care unit (ICU) between August 12 and September 12, 2020 with confirmed COVID-19 pneumonia and rapidly evolving ARF requiring oxygen support therapy and/or mechanical ventilation was retrospectively analyzed. We examined whether intravenous administration of tocilizumab, a monoclonal interleukin-6 receptor antibody, was associated with improved outcome. All patients received empiric antivirals, dexamethasone 6 mg/day for 7 days, antibiotics, and prophylactic anticoagulation. Tocilizumab was administered at a dosage of 8 mg/kg [two consecutive intravenous infusions 12 h apart]. Outcome measures such as mortality on day-14, ICU length of stay, and rate of nosocomial acquired bacterial infections were also analyzed. Results: Patients were males (88.2%) aged 51 [interquartile range (IQR): 42.5-58.75)], with admission Acute Physiology and Chronic Health Evaluation (APACHE) 4 score of 53 (IQR: 37.75-72.5), and had more than one comorbidity (62.3%). On admission, twenty nine patients (47.5%) were mechanically ventilated, and thirty two patients (52.5%) were receiving oxygen therapy. No serious adverse effects due to tocilizumab therapy were recorded. However, twelve patients (19.6%) developed nosocomial acquired infections. ICU length of stay was 13 (IQR: 9-17) days, and mortality on day-14 was 24.6%. Six patients were shifted to other hospitals but were followed-up. The overall mortality on day-30 was 31.1%. Non-mechanically ventilated patients had higher survival rates compared to mechanically ventilated patients although results were not significant [hazards ratio = 2.6 (95% confidence intervals: 0.9-7.7), p = 0.08]. Tocilizumab did not affect the mortality of critically ill COVID-19 patients. CONCLUSION: Tocilizumab could be an adjunct safe therapy in rapidly evolving COVID-19 pneumonia and associated critical illness.

COVID-19 in a patient with a flare of systemic lupus erythematosus: A rare case-report.

This is a rare case-report of a young female with systemic lupus erythematosus and end-stage kidney disease (on maintenance hemodialysis) who was admitted to our intensive care unit due to life-threatening COVID-19. The patient was diagnosed with a flare of lupus; while being on maintenance hydroxychloroquine therapy. However, after the administration of steroids she made an uneventful recovery and was discharged home. In this report, the diagnostic dilemmas and the therapeutic challenges due to the overlapping clinical, imaging, and laboratory findings between lupus and COVID-19 pneumonitis are outlined. In conclusion, patients with lupus may be affected by COVID-19 despite the administration of hydroxychloroquine. The administration of steroids may have a beneficial effect on mitigating both the flare of SLE and the COVID-19 associated hyperinflammation.

Co-infection of SARS-CoV-2 and Bordetella bronchiseptica in a young man with idiopathic non-cystic bronchiectasis and vitamin D3 deficiency.

This is the first reported case, to our knowledge, of co-infection of Bordetella bronchiseptica and SARS-CoV-2 in a young patient with underlying idiopathic bronchiectasis and vitamin D3 deficiency that was treated successfully with a combination therapeutic regime integrating doxycycline, empiric therapies for COVID-19, vitamin D supplementation, and supportive ICU care. Large prospective studies are required to investigate further the role of co-infections in COVID-19 patients with bronchiectasis. Randomized control trials should examine the putative beneficial role of vitamin D supplementation in patients with COVID-19.

Insidious development of pulmonary embolism in asymptomatic patients with COVID-19: Two rare case-reports.

Scarce data exist regarding the clinical sequelae of COVID-19 and/or the prevalence of thromboembolic disease in asymptomatic patients. Surely, there is increased prevalence of thromboembolic disease and pulmonary embolism (PE) in critically ill patients with COVID-19; hence the administration of even enhanced thromboprophylaxis was suggested. However, the administration of regular thromboprophylaxis in asymptomatic outpatients is an entirely different matter. Herein, we present the clinical story of insidious PE development in two asymptomatic COVID-19 female patients. Issues regarding the pathogenesis of thromboembolism in COVID-19 and the clinical management are equally discussed.

COVID-19 in a patient with active tuberculosis: A rare case-report.

Scarce data exist about the clinical features of COVID-19 in patients with concomitant active and/or latent tuberculosis (TB). This rare case-report outlines the diagnosis, management and outcome of a sixty year old hypertensive and diabetic patient with serious COVID-19 pneumonia and underlying active TB. The patient was treated successfully in a COVID-19 designated intensive care unit in Saudi Arabia.

Modified Early Warning Score as a predictor of intensive care unit readmission within 48 hours: a retrospective observational study. / Modified Early Warning Score como preditor de readmissão à unidade de terapia intensiva dentro de 48 horas: um estudo observacional retrospectivo.

OBJECTIVE: To evaluate the hypothesis that the Modified Early Warning Score (MEWS) at the time of intensive care unit discharge is associated with readmission and to identify the MEWS that most reliably predicts intensive care unit readmission within 48 hours of discharge. METHODS: This was a retrospective observational study of the MEWSs of discharged patients from the intensive care unit. We compared the demographics, severity scores, critical illness characteristics, and MEWSs of readmitted and non-readmitted patients, identified factors associated with readmission in a logistic regression model, constructed a Receiver Operating Characteristic (ROC) curve of the MEWS in predicting the probability of readmission, and presented the optimum criterion with the highest sensitivity and specificity. RESULTS: The readmission rate was 2.6%, and the MEWS was a significant predictor of readmission, along with intensive care unit length of stay > 10 days and tracheostomy. The ROC curve of the MEWS in predicting the readmission probability had an AUC of 0.82, and a MEWS > 6 carried a sensitivity of 0.78 (95%CI 0.66 - 0.9) and specificity of 0.9 (95%CI 0.87 - 0.93). CONCLUSION: The MEWS is associated with intensive care unit readmission, and a score > 6 has excellent accuracy as a prognostic predictor.

Modified Early Warning Score como preditor de readmissão à unidade de terapia intensiva dentro de 48 horas: um estudo observacional retrospectivo / Modified Early Warning Score as a predictor of intensive care unit readmission within 48 hours: a retrospective observational study

RESUMO Objetivo: Avaliar a hipótese de que o Modified Early Warning Score (MEWS) por ocasião da alta da unidade de terapia intensiva associa-se com readmissão, e identificar o nível desse escore que prediz com maior confiabilidade a readmissão à unidade de terapia intensiva dentro de 48 horas após a alta. Métodos: Este foi um estudo observacional retrospectivo a respeito do MEWS de pacientes que receberam alta da unidade de terapia intensiva. Comparamos dados demográficos, escores de severidade, características da doença crítica e MEWS de pacientes readmitidos e não readmitidos. Identificamos os fatores associados com a readmissão em um modelo de regressão logística. Construímos uma curva Característica de Operação do Receptor para o MEWS na predição da probabilidade de readmissão. Por fim, apresentamos o critério ideal com maior sensibilidade e especificidade. Resultados: A taxa de readmissões foi de 2,6%, e o MEWS foi preditor significante de readmissão, juntamente do tempo de permanência na unidade de terapia intensiva acima de 10 dias e traqueostomia. A curva Característica de Operação do Receptor relativa ao MEWS para predizer a probabilidade de readmissão teve área sob a curva de 0,82, e MEWS acima de 6 teve sensibilidade de 0,78 (IC95% 0,66 - 0,9) e especificidade de 0,9 (IC95% 0,87 - 0,93). Conclusão: O MEWS associa-se com readmissão à unidade de terapia intensiva, e o escore acima de 6 teve excelente precisão como preditor prognóstico.

ABSTRACT Objective: To evaluate the hypothesis that the Modified Early Warning Score (MEWS) at the time of intensive care unit discharge is associated with readmission and to identify the MEWS that most reliably predicts intensive care unit readmission within 48 hours of discharge. Methods: This was a retrospective observational study of the MEWSs of discharged patients from the intensive care unit. We compared the demographics, severity scores, critical illness characteristics, and MEWSs of readmitted and non-readmitted patients, identified factors associated with readmission in a logistic regression model, constructed a Receiver Operating Characteristic (ROC) curve of the MEWS in predicting the probability of readmission, and presented the optimum criterion with the highest sensitivity and specificity. Results: The readmission rate was 2.6%, and the MEWS was a significant predictor of readmission, along with intensive care unit length of stay > 10 days and tracheostomy. The ROC curve of the MEWS in predicting the readmission probability had an AUC of 0.82, and a MEWS > 6 carried a sensitivity of 0.78 (95%CI 0.66 - 0.9) and specificity of 0.9 (95%CI 0.87 - 0.93). Conclusion: The MEWS is associated with intensive care unit readmission, and a score > 6 has excellent accuracy as a prognostic predictor.