Efficacy and Outcome of Remdesivir and Tocilizumab Combination Against Dexamethasone for the Treatment of Severe COVID-19: A Randomized Controlled Trial

Chowdhury, Abu Taiub Mohammed Mohiuddin; Kamal, Aktar; Abbas, Kafil Uddin; Talukder, Shubhashis; Karim, Md. Rezaul; Ali, Md. Ahsan; Nuruzzaman, Md.; Li, Yarui; He, Shuixiang

doi:10.3389/fphar.2022.690726

Cited by 16 publications

(12 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their identification and the volumetric quantification may allow an easier classification in terms of gravity, extent and progression of the disease. Moreover, this may provide a high-impact tool to enhance awareness of the severity of COVID-19 pneumonia [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Section: Introductionmentioning

confidence: 99%

Imaging Severity COVID-19 Assessment in Vaccinated and Unvaccinated Patients: Comparison of the Different Variants in a High Volume Italian Reference Center

Granata

Fusco

Villanacci

et al. 2022

JPM

View full text Add to dashboard Cite

Purpose: To analyze the vaccine effect by comparing five groups: unvaccinated patients with Alpha variant, unvaccinated patients with Delta variant, vaccinated patients with Delta variant, unvaccinated patients with Omicron variant, and vaccinated patients with Omicron variant, assessing the “gravity” of COVID-19 pulmonary involvement, based on CT findings in critically ill patients admitted to Intensive Care Unit (ICU). Methods: Patients were selected by ICU database considering the period from December 2021 to 23 March 2022, according to the following inclusion criteria: patients with proven Omicron variant COVID-19 infection with known COVID-19 vaccination with at least two doses and with chest Computed Tomography (CT) study during ICU hospitalization. Wee also evaluated the ICU database considering the period from March 2020 to December 2021, to select unvaccinated consecutive patients with Alpha variant, subjected to CT study, consecutive unvaccinated and vaccinated patients with Delta variant, subjected to CT study, and, consecutive unvaccinated patients with Omicron variant, subjected to CT study. CT images were evaluated qualitatively using a severity score scale of 5 levels (none involvement, mild: ≤25% of involvement, moderate: 26–50% of involvement, severe: 51–75% of involvement, and critical involvement: 76–100%) and quantitatively, using the Philips IntelliSpace Portal clinical application CT COPD computer tool. For each patient the lung volumetry was performed identifying the percentage value of aerated residual lung volume. Non-parametric tests for continuous and categorical variables were performed to assess statistically significant differences among groups. Results: The patient study group was composed of 13 vaccinated patients affected by the Omicron variant (Omicron V). As control groups we identified: 20 unvaccinated patients with Alpha variant (Alpha NV); 20 unvaccinated patients with Delta variant (Delta NV); 18 vaccinated patients with Delta variant (Delta V); and 20 unvaccinated patients affected by the Omicron variant (Omicron NV). No differences between the groups under examination were found (p value > 0.05 at Chi square test) in terms of risk factors (age, cardiovascular diseases, diabetes, immunosuppression, chronic kidney, cardiac, pulmonary, neurologic, and liver disease, etc.). A different median value of aerated residual lung volume was observed in the Delta variant groups: median value of aerated residual lung volume was 46.70% in unvaccinated patients compared to 67.10% in vaccinated patients. In addition, in patients with Delta variant every other extracted volume by automatic tool showed a statistically significant difference between vaccinated and unvaccinated group. Statistically significant differences were observed for each extracted volume by automatic tool between unvaccinated patients affected by Alpha variant and vaccinated patients affected by Delta variant of COVID-19. Good statistically significant correlations among volumes extracted by automatic tool for each lung lobe and overall radiological severity score were obtained (ICC range 0.71–0.86). GGO was the main sign of COVID-19 lesions on CT images found in 87 of the 91 (95.6%) patients. No statistically significant differences were observed in CT findings (ground glass opacities (GGO), consolidation or crazy paving sign) among patient groups. Conclusion: In our study, we showed that in critically ill patients no difference were observed in terms of severity of disease or exitus, between unvaccinated and vaccinated patients. The only statistically significant differences were observed, with regard to the severity of COVID-19 pulmonary parenchymal involvement, between unvaccinated patients affected by Alpha variant and vaccinated patients affected by Delta variant, and between unvaccinated patients with Delta variant and vaccinated patients with Delta variant.

show abstract

Section: Introductionmentioning

confidence: 99%

Imaging Severity COVID-19 Assessment in Vaccinated and Unvaccinated Patients: Comparison of the Different Variants in a High Volume Italian Reference Center

Granata

Fusco

Villanacci

et al. 2022

JPM

View full text Add to dashboard Cite

show abstract

“…Detecting ANS dysfunction in patients with severe COVID-19 is especially relevant since more therapies are becoming available for the treatment of COVID-19 patients and efficient distribution to those who need them most is crucial. Specific therapies include remdesivir, anti-interleukin-6 receptor antibodies, Janus kinase inhibitors [ 28 , 29 ] as well as the microtubule disruptor sabizabulin [ 30 ] which has shown promising results in a recent phase II clinical trial in reducing mortality and respiratory failure. In addition to the potential prognostic value, our findings suggest that autonomic dysfunction itself increases mortality and could be an interesting target for therapeutic interventions for example in form of vagal nerve stimulation or adaptation of management of fluid therapy, mechanical ventilation, or use of vasopressors.…”

Section: Discussionmentioning

confidence: 99%

Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit

Woo

Mayer

Fischer

et al. 2023

Neurol. Res. Pract.

View full text Add to dashboard Cite

Background Unpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown. Methods We retrospectively analyzed data collected during a single-center observational study (March 2020–November 2021) which was performed at the University Medical Center Hamburg-Eppendorf, a large tertiary medical center in Germany. All patients admitted to ICU due to acute COVID-19 disease during the study period were included (n = 361). Heart rate variability (HRV) and blood pressure variability (BPV) per day were used as clinical surrogates of dysautonomia and compared between survivors and non-survivors at different time points after admission. Intraindividual correlation of vital signs with laboratory parameters were calculated and corrected for age, sex and disease severity. Results Patients who deceased in ICU had a longer stay (median days ± IQR, survivors 11.0 ± 27.3, non-survivors 14.1 ± 18.7, P = 0.85), in contrast time spent under invasive ventilation was not significantly different (median hours ± IQR, survivors 322 ± 782, non-survivors 286 ± 434, P = 0.29). Reduced HRV and BPV predicted lethal outcome in patients staying on ICU longer than 10 days after adjustment for age, sex, and disease severity. Accordingly, HRV was significantly less correlated with inflammatory markers (e.g. CRP and Procalcitonin) and blood carbon dioxide in non-survivors in comparison to survivors indicating uncoupling between autonomic function and inflammation in non-survivors. Conclusions Our study suggests autonomic dysfunction as a contributor to mortality in critically ill COVID-19 patients during the first waves of the pandemic. Serving as a surrogate for disease progression, these findings could contribute to the clinical management of COVID-19 patients admitted to the ICU. Furthermore, the suggested measure of dysautonomia and correlation with other laboratory parameters is non-invasive, simple, and cost-effective and should be evaluated as an additional outcome parameter in septic patients treated in the ICU in the future.

show abstract

“…Antibodies can control virus-induced cytokine storm (tocilizumab, secukinumab) or directly target S protein and inhibit virus entry (casirivimab, imdevimab). The administration of monoclonal antibodies has been associated with reduced mortality rates and shorter hospital stays [ 94 , 95 ]. Some of the presented agents are known drugs used in the treatment of other diseases, such as metformin (DM2) or tranilast (asthma), while others are plant derivatives with multiple beneficial effects (resveratrol, sulforaphane).…”

Section: Discussionmentioning

confidence: 99%

How to Restore Oxidative Balance That Was Disrupted by SARS-CoV-2 Infection

Kiełbowski

Herian

Pawlik

2022

IJMS

View full text Add to dashboard Cite

Coronavirus 2019 disease (COVID-19) is caused by different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December of 2019. COVID-19 pathogenesis is complex and involves a dysregulated renin angiotensin system. Severe courses of the disease are associated with a dysregulated immunological response known as cytokine storm. Many scientists have demonstrated that SARS-CoV-2 impacts oxidative homeostasis and stimulates the production of reactive oxygen species (ROS). In addition, the virus inhibits glutathione (GSH) and nuclear factor erythroid 2-related factor 2 (NRF2)—a major antioxidant which induces expression of protective proteins and prevents ROS damage. Furthermore, the virus stimulates NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes which play a significant role in inducing a cytokine storm. A variety of agents with antioxidant properties have shown beneficial effects in experimental and clinical studies of COVID-19. This review aims to present mechanisms of oxidative stress induced by SARS-CoV-2 and to discuss whether antioxidative drugs can counteract detrimental outcomes of a cytokine storm.

show abstract

Efficacy and Outcome of Remdesivir and Tocilizumab Combination Against Dexamethasone for the Treatment of Severe COVID-19: A Randomized Controlled Trial

Cited by 16 publications

References 34 publications

Imaging Severity COVID-19 Assessment in Vaccinated and Unvaccinated Patients: Comparison of the Different Variants in a High Volume Italian Reference Center

Imaging Severity COVID-19 Assessment in Vaccinated and Unvaccinated Patients: Comparison of the Different Variants in a High Volume Italian Reference Center

Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit

How to Restore Oxidative Balance That Was Disrupted by SARS-CoV-2 Infection

Contact Info

Product

Resources

About