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.