Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial.

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.

Darunavir-cobicistat versus lopinavir-ritonavir in the treatment of COVID-19 infection (DOLCI): A multicenter observational study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. METHODS AND FINDINGS: This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. CONCLUSION: In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04425382.

Case Report: COVID-19-Associated Bilateral Spontaneous Pneumothorax-A Literature Review.

COVID-19 is a pandemic caused by SARS-CoV-2, primarily affecting the respiratory tract. Pulmonary complications of COVID-19 may include acute respiratory distress syndrome and pulmonary embolism. Pneumothorax has been recently reported in association with COVID-19. We report a case of COVID-19 pneumonia with bilateral spontaneous pneumothorax with no known underlying lung disease or risk factors.