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.

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.

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.

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.

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.

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.