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.

Early Versus Late DNR Orders and its Predictors in a Saudi Arabian ICU: A Descriptive Study.

Background: Practices of Do-Not-Resuscitate (DNR) orders show discrepancies worldwide, but there are only few such studies from Saudi Arabia. Objective: To describe the practice of DNR orders in a Saudi Arabian tertiary care ICU. Methods: This retrospective study included all patients who died with a DNR order at the ICU of King Saud Medical City, Riyadh, Saudi Arabia, between January 1 to December 31, 2021. The percentage of early DNR (i.e., ≤48 hours of ICU admission) and late DNR (>48 hours) orders were determined and the variables between the two groups were compared. The determinants of late DNR were also investigated. Results: A total of 723 cases met the inclusion criteria, representing 14.9% of all ICU discharges and 63% of all ICU deaths during the study period. The late DNR group comprised the majority of the cases (78.3%), and included significantly more patients with acute respiratory distress syndrome (ARDS), community acquired pneumonia (CAP), acute kidney injury, and COVID-19, and significantly fewer cases of readmissions and malignancies. Septic shock lowered the odds of a late DNR (OR = 0.4, 95% CI: 0.2-0.9;P= 0.02), while ARDS (OR = 3.3, 95% CI: 2-5.4;P < 0.001), ischemic stroke (OR = 2.5, 95% CI: 1.1-5.4;P= 0.02), and CAP (OR = 2, 95% CI: 1.3-3.1;P= 0.003) increased the odds of a late DNR. Conclusion: There was a higher frequency of late DNR orders in our study compared to those reported in several studies worldwide. Cases with potential for a favorable outcome were more likely to have a late DNR order, while those with expected poorer outcomes were more likely to have an early DNR order. The discrepancies highlight the need for clearer guidelines to achieve consistency.