AimTo assess the efficacy and safety of favipiravir in adults with moderate to severe coronavirus disease 2019 (COVID-19).MethodsIn this randomized, double-blind, multicenter, phase 3 trial, adults (21-80 years) with real-time reverse transcriptase polymerase chain reaction (rRT-PCR) confirmed SARS-CoV-2 infection and presenting with moderate to severe COVID-19 and requiring hospitalization were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-10: 800 mg BID) (FPV) plus standard supportive care (SoC) versus placebo plus SoC (placebo). The primary endpoint was time to resolution of hypoxia.ResultsIn total, 353 patients were randomized to receive either FPV or placebo (175 and 178 in the FPV and placebo groups, respectively). Overall, 76% of the patients (240/315, 78% in FPV vs. 75% in placebo group) reached resolution of hypoxia on or before day 28. The median time to resolution of hypoxia was 7 days in the FPV group and 8 days in the placebo group. Treatment effect was not significant [Hazard ratio (HR) (95% CI): 0.991 (0.767, 1.280) (p=0.94)].Patients in the lower NEWS-2 clinical risk subgroup were more likely to achieve shorter time to resolution of hypoxia with the median time to resolution of hypoxia of 6 days in FPV and 7 days in placebo group [HR (95% CI): 1.21 (0.847, 1.731) (p=0.29)]; shorter time to hospital discharge with a median time to discharge of 8 and 10 days in the FPV and placebo group, respectively [HR (95% CI): 1.47 (1.081, 1.997) (p=0.014)]; and shorter time to improvement by 1-point improvement over baseline in WHO 10-point clinical status score with the median time to improvement by 1-point from baseline of 6 and 7 days in the FPV and placebo group, respectively [HR (95% CI): 1.16 (0.830, 1.624) (p=0.38)] than higher NEWS-2 clinical risk subgroup.Treatment emergent adverse event (TEAEs) were experienced by 62/334 (19%) patients [35/168 (21%) patients in FPV and 27/166 (16%) in placebo group]. Hyperuricaemia/increased blood uric acid was reported in 9 (3%)/2 (1%) patients [8 (5%)/1(1%) patients in FPV and 1 (1%)/1(1%) in placebo group], which were of mild intensity and transient. Overall, 36 serious adverse events (SAEs) were reported, 20 in FPV and 16 in placebo group.ConclusionThe trial did not find favipiravir to be effective in moderate to severe, hospitalized COVID-19 patients; favourable clinical trends were observed in patients with lower NEWS-2 risk when early administration of favipiravir could be achieved.

Background This study aims to examine risk factors and complications associated with bleeding events in patients with COVID-19 who are on anticoagulation. Material and methods We conducted retrospective review of all patients who were admitted with COVID-19 and developed bleeding events between March and June 2020. Data were analyzed in accordance with three major outcomes. Mortality within 30 days of bleeding episode, resolution of the bleeding event, and the type of bleeding event. Results Of 122 bleeds, there was 55 (28 %) gastrointestinal (GI) bleeds. Overall mortality was 59 % (n = 72). The prevalence of therapeutic invasive interventions was 11.5 % (n = 14) all were successful in resolving the bleeding event. We found that having a GI bleeds was associated with higher risk of mortality compared to non-GI bleeds (p = 0.04) and having occult bleeds to be associated with 15 times increased risk of mortality (OR 15, 95%CI 1.97–29.1, p = 0.01). Furthermore, patients who were on no anticoagulation (none) (OR 0.1, 95%CI 0.01–0.86, p < 0.00), on prophylactic dose anticoagulation (OR 0.07, 95%CI 0.02–0.28, p = 0.03) or intermediate dose anticoagulation (OR 0.36, 95%CI 0.09–1.34, p = 0.13) were less likely to die than patients on therapeutic dose. Conclusions The best approach to manage COVID-19 bleeding patients is to prioritize therapies that manage sepsis induce coagulopathy and shock over other approaches. In COVID-19 patients’ routine prescription of supra-prophylactic dose anticoagulation should be revisited and more individualized approach to prescription should be the norm. Regardless of the cause of bleeding event it appears that the majority of bleeding events resolve with noninvasive interventions and when invasive interventions were necessary, they were associated with high success rate despite the delay.

Background: Nucleotide-binding oligomerization domain-containing two ( NOD2 / CARD15 ) gene polymorphisms are implicated in the pathogenesis of Crohn's disease (CD). Aim: To describe the allelic frequency of NOD2 / CARD15 gene variants among Kuwaiti patients with CD and investigate potential genotype/phenotype associations. Methods: Adult Kuwaiti citizens with an established diagnosis of CD and healthy controls were enrolled from October 2018 to May 2020. Three common NOD2 / CARD15 polymorphisms (R702W, G908R, and L1007fs) and P268S and IVS8 +158 polymorphisms were screened by polymerase chain reaction/restriction analysis length polymorphism (PCR/RFLP). Results: Ninety adult Kuwaiti patients with CD and 210 healthy subjects (as controls) were recruited. P268S, IVS8 +158 , G908R, and R702W minor alleles were identified in 38.9%, 21.1%, 12.2%, and 4.4% of CD patients, respectively. NOD2 / CARD15 polymorphisms coexisted in 35 healthy controls (16.7%) and 21 CD patients (23.3%). Individuals with either a single or multiple polymorphism were approximately two times more likely to have CD than those with no polymorphism. Patients with multiple polymorphisms had significantly more stricturing and penetrating disease. Conclusion: NOD2 / CARD15 gene polymorphisms were significantly associated with an increased risk of disease and aggressive phenotypes among the Kuwaiti CD population.

Purpose This cross-sectional observational study aims to report preliminary data from the first experience using tocilizumab for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in three of Kuwait’s largest public hospitals City. Patients and methods This chart review study examined the benefits of tocilizumab treatment among 127 patients diagnosed with severe coronavirus disease of 2019 (COVID-19) pneumonia. Results 90 of 127 patients (71%) survived. Mortality was highest in the elderly with multiple medical conditions. Conclusion Despite the small sample size and retrospective nature of the work, our findings are consistent with recent studies suggesting tocilizumab administration in patients presenting with severe COVID pneumonia with associated hyperinflammatory features conferred mortality benefit.