The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies.

OBJECTIVES: This study aimed to evaluate the efficacy and adverse events of favipiravir in patients with COVID-19. METHODS: Our protocol was registered on PROSPERO (CRD42020206305). Fourteen databases were searched until February 8th, 2021. An update search for new RCTs was done on March 2nd, 2022. Meta-analysis was done for randomized controlled trials (RCTs) and non-RCTs. RESULTS: Overall, 157 studies (24 RCTs, 1 non-RCT, 21 observational studies, 2 case series, and 106 case reports) were included. On hospitalized patients, in comparison to standard of care, favipiravir showed a higher rate of viral clearance at day 5 (RR = 1.60, p = 0.02), defervescence at day 3-4 (RR = 1.99, p <0.01), chest radiological improvement (RR = 1.33, p <0.01), hospital discharge at day 10-11 (RR = 1.19, p <0.01), and shorter clinical improvement time (MD = -1.18, p = 0.05). Regarding adverse events, favipiravir groups had higher rates of hyperuricemia (RR = 9.42, p <0.01), increased alanine aminotransferase (RR = 1.35, p <0.01) but lower rates of nausea (RR = 0.42, p <0.01) and vomiting (R R= 0.19, p=0.02). There were no differences regarding mortality (RR=1.19, p=0.32), and increased aspartate aminotransferase (RR = 1.11, p = 0.25). On nonhospitalized patients, no significant differences were reported. CONCLUSIONS: Adding favipiravir to the standard of care provides better outcomes for hospitalized patients with COVID-19. Pregnant, lactating women, and patients with a history of hyperuricemia should avoid using favipiravir.

Biofilm development of an opportunistic model bacterium analysed at high spatiotemporal resolution in the framework of a precise flow cell.

Life of bacteria is governed by the physical dimensions of life in microscales, which is dominated by fast diffusion and flow at low Reynolds numbers. Microbial biofilms are structurally and functionally heterogeneous and their development is suggested to be interactively related to their microenvironments. In this study, we were guided by the challenging requirements of precise tools and engineered procedures to achieve reproducible experiments at high spatial and temporal resolutions. Here, we developed a robust precise engineering approach allowing for the quantification of real-time, high-content imaging of biofilm behaviour under well-controlled flow conditions. Through the merging of engineering and microbial ecology, we present a rigorous methodology to quantify biofilm development at resolutions of single micrometre and single minute, using a newly developed flow cell. We designed and fabricated a high-precision flow cell to create defined and reproducible flow conditions. We applied high-content confocal laser scanning microscopy and developed image quantification using a model biofilm of a defined opportunistic strain, Pseudomonas putida OUS82. We observed complex patterns in the early events of biofilm formation, which were followed by total dispersal. These patterns were closely related to the flow conditions. These biofilm behavioural phenomena were found to be highly reproducible, despite the heterogeneous nature of biofilm.