Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Anti-IgE monoclonal antibodies as potential treatment in COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system plays a key role in the survival of patients to viral infections, in COVID-19, there is a hyperinflammatory immune response evoked by all the immune cells, such as neutrophils, monocytes, and includes release of various cytokines, resulting in an exaggerated immune response, named cytokine storm. This severe, dysregulated immune response causes multi-organ damage, which eventually leads to high mortality. One of the most important components of hypersensitivity is immunoglobulin E (IgE), which plays a major role in susceptibility to respiratory infections and can lead to the activation of mast cells. There is also a negative association between IgE and IFN-α, which can reduce Toll-like receptor (TLR) nine receptor expression and TLR-7 signaling to disrupt IFN production. Moreover, anti-IgE drugs such as omalizumab reduces the severity and duration of COVID-19. In addition to its anti-IgE effect, omalizumab inhibits inflammatory cells such as neutrophils. Hence, blockade of IgE may have clinical utility as an immunotherapy for COVID-19.

Superior Mesenteric Venous (SMV) Thrombosis Accompanied with Appendicitis in a Patient with Primary Diagnosis of Typhoid Fever.

BACKGROUND: Septic thrombophlebitis of the Superior Mesenteric Venous (SMV) is rarely accompanied by appendicitis, and symptoms are atypical, so the diagnosis is commonly delayed, resulting in it is associated with high mortality. CASE PRESENTATION: We report a case of neglected SMV septic thrombophlebitis is caused by appendicitis. The patient represented with fever, vague abdominal pain without rebound tenderness, and history of the consumption of contaminated water. Antibiotic initiated due to suspicious typhoid fever. Then typhoid fever was ruled out. Computed tomography (CT) scans revealed micro-abscess forming complicated appendicitis and the thrombus in SMV. DISCUSSION AND CONCLUSION: The patient underwent a laparoscopic appendectomy, during which retrocecal gangrened perforated appendix with a 2×2 cm abscess was drained. Based on positive culture with ESBL organism meropenem was initiated. Appendectomy and treatment with broad- -spectrum antibiotics and anticoagulation led to a full recovery.

Thiamine for Prevention of Postoperative Delirium in Patients Undergoing Gastrointestinal Surgery: A Randomized Clinical Trial.

OBJECTIVE: Postoperative delirium is a common complication after gastrointestinal surgery that is associated with adverse outcomes. Thiamine is an essential cofactor for the glycolysis, oxidative metabolism, production of neurotransmitters in the crebs cycle. In this study, efficacy of thiamine was assessed as a preventive strategy of delirium in patients undergoing gastrointestinal surgery. METHODS: In this randomized clinical trial, 96 adult patients admitted to the intensive care unit (ICU) following gastrointestinal surgery were included. Patients were allocated to receive either 200 mg intravenous thiamine daily or an equal volume of 0.9% saline for 3 days. Delirium was evaluated twice daily based on the confusion assessment method-ICU. The incidence of postoperative delirium was considered as the primary outcome, and total analgesic use and ventilation days has been defined as secondary outcomes of the study. FINDINGS: The incidence rate of delirium was significantly lower in the thiamine group than the placebo group on the first day (8.3% vs. 25%; Odds ratio: 0.27 [95% confidence interval (CI): 0.08-0.92]; P= 0.026) and on the second day (4.2% vs. 20.8%; or: 0.16 [95% CI: 0.03-0.81]; P= 0.014). No adverse effect related to thiamine was detected during the study course. CONCLUSION: Study results suggest that thiamine is a safe option for the prevention of postoperative delirium in patients after gastrointestinal surgery.