Remdesivir for Patients Hospitalized with COVID-19 Severe Pneumonia: A National Cohort Study (Remdeco-19).

BACKGROUND: Given the rapidly evolving pandemic of COVID-19 in 2020, authorities focused on the repurposing of available drugs to develop timely and cost-effective therapeutic strategies. Evidence suggested the potential utility of remdesivir in the framework of an early access program. REMDECO-19 is a multicenter national cohort study assessing the ability of remdesivir to improve the outcome of patients hospitalized with COVID-19. METHODS: We conducted a retrospective real-life study that included all patients from the early access program of remdesivir in France. The primary endpoint was the clinical course evolution of critically ill and hospitalized COVID-19 patients treated with remdesivir. Secondary endpoints were the SOFA score evolution within 29 days following the admission and mortality at 29 and 90 days. RESULTS: Eighty-five patients were enrolled in 22 sites from January to April 2020. The median WHO and SOFA scores were respectively reduced by two and six points between days 1 and 29. Improvement in the WHO-CPS and the SOFA score were observed in 83.5% and 79.3% of patients, respectively, from day 10. However, there was no effect of remdesivir on the 90-day survival based on the control cohort for hospitalized COVID-19 patients with invasive ventilation. CONCLUSIONS: SOFA score appeared to be an attractive approach to assess remdesivir efficacy and stratify its utilization or not in critically ill patients with COVID-19. This study brings a new clinical benchmark for therapeutic decision making and supports the use of remdesivir for some hospitalized COVID-19 patients.

Patients with Hematological Malignancies Treated with T-Cell or B-Cell Immunotherapy Remain at High Risk of Severe Forms of COVID-19 in the Omicron Era.

BACKGROUND: Patients with hematological malignancies are at greater risk of severe COVID-19 and have been prioritized for COVID-19 vaccination. A significant proportion of them have an impaired vaccine response, both due to the underlying disease and to the treatments. METHODS: We conducted a prospective observational study to identify the specific risks of the outpatient population with hematological diseases. RESULT: Between 22 December 2021 to 12 February 2022, we followed 338 patients of which 16.9% (n = 57) developed SARS-CoV-2 infection despite previous vaccination (94.7%). COVID-19 patients were more likely to have received immunotherapy (85.5% vs. 41%, p < 10-4), and particularly anti-CD20 monoclonal antibodies (40% vs. 14.9%, p < 10-4) and Bruton's tyrosine kinase inhibitors (BTKi) (7.3% vs. 0.7%, p < 10-2). There was no significant difference in demographic characteristics or hematological malignancies between COVID-19-positive and non-positive patients. Patients hospitalized for COVID-19 had more frequently received immunotherapy than patients with asymptomatic or benign forms (100% vs. 77.3%, p < 0.05). Hospitalized COVID-19 patients had a higher proportion of negative or weakly positive serologies than non-hospitalized patients (92.3% vs. 61%, p < 0.05). Patients who received tixagevimab/cilgavimab prophylaxis (n = 102) were less likely to be COVID-19-positive (4.9 vs. 22%, p < 0.05) without significant difference in hospitalization rates. CONCLUSION: In the immunocompromised population of patients with hematological malignancies, the underlying treatment of blood cancer by immunotherapy appears to be a risk factor for SARS-CoV-2 infection and for developing a severe form.

Plasma Concentrations and Safety of Lopinavir/Ritonavir in COVID-19 Patients.

BACKGROUND: Although the efficacy of lopinavir/ritonavir has not been proven, it has been proposed as an off-label treatment for COVID-19. Previously, it has been reported that the plasma concentrations of lopinavir significantly increase in inflammatory settings. As COVID-19 may be associated with major inflammation, assessing the plasma concentrations and safety of lopinavir in COVID-19 patients is essential. METHODS: Real-world COVID-19 data based on a retrospective study. RESULTS: Among the 31 COVID-19 patients treated with lopinavir/ritonavir between March 18, 2020 and April 1, 2020, higher lopinavir plasma concentrations were observed, which increased by 4.6-fold (interquartile range: 3.6-6.2), compared with the average plasma concentrations in HIV. Lopinavir concentrations in all except one patient were above the upper limit of the concentration range of HIV treatment. Approximately one to 5 patients prematurely stopped treatment mainly because of an ADR related to hepatic or gastrointestinal disorders. CONCLUSIONS: Lopinavir plasma concentrations in patients with moderate-to-severe COVID-19 were higher than expected, and they were associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, a high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2, as suggested by previous studies. Therefore, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Caution is essential because off-label use can be associated with a new drug safety profile.

Cancer, immune suppression and Coronavirus Disease-19 (COVID-19): Need to manage drug safety (French Society for Oncology Pharmacy [SFPO] guidelines).

The Coronavirus disease (COVID-19) pandemic is disrupting our health environment. As expected, studies highlighted the great susceptibility of cancer patients to COVID-19 and more severe complications, leading oncologists to deeply rethink patient cancer care. This review is dedicated to the optimization of care pathways and therapeutics in cancer patients during the pandemic and aims to discuss successive issues. First we focused on the international guidelines proposing adjustments and alternative options to cancer care in order to limit hospital admission and cytopenic treatment in cancer patients, most of whom are immunocompromised. In addition cancer patients are prone to polypharmacy, enhancing the risk of drug-related problems as adverse events and drug-drug interactions. Due to increased risk in case of COVID-19, we reported a comprehensive review of all the drug-related problems between COVID-19 and antineoplastics. Moreover, in the absence of approved drug against COVID-19, infected patients may be included in clinical trials evaluating new drugs with a lack of knowledge, particularly in cancer patients. Focusing on the several experimental drugs currently being evaluated, we set up an original data board helping oncologists and pharmacists to identify promptly drug-related problems between antineoplastics and experimental drugs. Finally additional and concrete recommendations are provided, supporting oncologists and pharmacists in their efforts to manage cancer patients and to optimize their treatments in this new era related to COVID-19.