Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status

Antinori, Spinello; Cossu, Maria Vittoria; Ridolfo, Anna Lisa; Rech, Roberto; Bonazzetti, Cecilia; Pagani, Gabriele; Gubertini, G.; Coen, Massimo; Magni, C.; Castelli, Antonio; Borghi, Beatrice; Colombo, Riccardo; Giorgi, Riccardo; Angeli, Elena; Mileto, Davide; Milazzo, Laura; Vimercati, Stefania; Pellicciotta, Martina; Corbellino, Mario; Torre, Alessandro; Rusconi, Stefano; Oreni, Letizia; Gismondo, Maria Rita; Giacomelli, Andrea; Meroni, Luca; Rizzardini, Giuliano; Galli, Massimo

doi:10.1016/j.phrs.2020.104899

Cited by 192 publications

(265 citation statements)

References 29 publications

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“…Antionori et al (329), analyzing patients with severe COVID-19 pneumonia in an intensive care unit (ICU) who were treated for 10 days with RDV, found that on the 28 th day, 38.9% showed improvement, 16.7% were still on mechanical ventilation, and 44.4% died. The data suggest that this treatment can benefit hospitalized patients who are not in the ICU, where the clinical result was better and adverse events are observed less frequently.…”

Section: Antiviralsmentioning

confidence: 99%

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

et al. 2020

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Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and mainly spreads through the respiratory tract, which it then uses to reach several organs. The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches.

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Section: Antiviralsmentioning

confidence: 99%

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

et al. 2020

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“…tality rate was similar to the placebo group (Antinori et al, 2020;Beigel et al, 2020;Grein et al, 2020;Wang et al, 2020). The antiviral activity of remdesivir is not only marginal but also variable.…”

Section: Fig 5 2d Ligplot Interaction Of Rutin Docked In To the At1mentioning

confidence: 54%

Current targets and drug candidates for prevention and treatment of SARS-CoV-2 (COVID-19) infection

Goyal¹,

Majeed²,

Tonk³

et al. 2020

Reviews in Cardiovascular Medicine

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Angiotensin-converting enzyme 2 (ACE2), the host cellbinding site for SAR-CoV-2, poses twofold drug development problems. First, the role of ACE2 itself is still a matter of investigation, and no specific drugs are available targeting ACE2. Second, as a consequence of SARS-CoV-2 interaction with ACE2, there is an impairment of the renin-angiotensin system (RAS) involved in the functioning of vital organs like the heart, kidney, brain, and lungs. In developing antiviral drugs for COVID-19, ACE2, RNAdependent RNA polymerase (RdRp), and the specific enzymes involved in the viral and cellular gene expression have been the primary targets. SARS-CoV-2 being a new virus with unusually high mortality, there has been a need to get medicines in an emergency, and the drug repurposing has been a primary strategy. Considering extensive mortality and morbidity throughout the world, we have made a maiden attempt to discover the drugs interacting with RAS and identify the lead compounds from herbal plants using molecular docking. Both host ACE2 and viral RNA-dependent RNA polymerase (RdRp) and ORF8 appear to be the primary targets for the treatment of COVID-19. While the drug repurposing of currently approved drugs seems to be one strategy for the treatment of COVID-19, purposing phytochemicals may be another essential strategy for discovering lead compounds. Using in silico molecular docking, we have identified a few phytochemicals that may provide insights into designing herbal and synthetic therapeutics to treat COVID-19.

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“…Introduction of antiviral drugs is a common cause of drug-induced AKI 46,47 . In the clinical experiment of Remdesivir, AKI as the most frequent adverse event lead to drug discontinuation 11,12 . Antiviral drugs cause AKI by many mechanisms including direct renal tubular toxicity, allergic interstitial nephritis, and crystal nephropathy 48,49 .…”

Section: Discussionmentioning

confidence: 99%

Whether Remdesivir Increases the Risk of Acute Kidney Injury (AKI) in Patients with COVID-19: A Systematic Review and Meta-Analysis

Xu¹,

Tang²,

Huang³

et al. 2020

Preprint

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Background: Acute kidney injury (AKI) occurs among patients with COVID-19, it is also proved to be associated with in-hospital mortality. Remdesivir, an RNA polymerase inhibitor, has shown its antiviral activity in vitro and animal models. The adverse effect of Remdesivir especially AKI is the most common cause which lead to drug discontinuation. Whether Remdesivir increases the risk of AKI in patients with COVID-19 is not clear. We conducted a systematic review and meta-analysis to evaluate the incidence rate of AKI in hospitalized COVID-19 patients and whether Remdesivir increases the risk of AKI. Methods: A thorough search was carried out to find relevant studies in PubMed, medRxiv, and Web of Science from 1 Jan 2020 till 1 June 2020. 15135 COVID-19 patients and 981 COVID-19 patients using Remdesivir were included in our meta-analysis. Results: The pooled estimated incidence of AKI in all hospitalized COVID-19 patients was 12.0% (95% CI:9.0%-15.0%). According to our subgroup study, the incidence of AKI was associated with the age, disease severity and race of patients. The incidence of AKI in hospitalized COVID-19 patients using Remdesivir was 6% (95% CI: 3%-13%) with a total of 5 studies. Comparing with COVID-19 patients without Remdesivir treatment, Remdesivir treatment do not increase the risk of AKI in COVID-19 patients showing OR 0.80(95%CI: 0.44-1.46, P>0.05). Conclusions: We found out that AKI was not rare in hospitalized COVID-19 patients. The incidence of AKI was associated with age, disease severity and race. Remdesivir treatment did not increase the risk of AKI in hospitalized COVID-19 patients. Our meta-analysis may provide an evidence for future study that AKI is associated with the natural cause of COVID-19, not the adverse event after the usage of Remdesivir.

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Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status

Cited by 192 publications

References 29 publications

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

Current targets and drug candidates for prevention and treatment of SARS-CoV-2 (COVID-19) infection

Whether Remdesivir Increases the Risk of Acute Kidney Injury (AKI) in Patients with COVID-19: A Systematic Review and Meta-Analysis

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