Remdesivir use in severe and critical COVID-19 patients might be associated with lower incidence of arterial thrombotic events

Lucijanić, Marko; Bistrović, Petra; Jordán, Ana; Mihaljević, Iva; Bukvić, Stela; Kovačević, Stjepan; Ranilović, D; Šakota, Sara; Glasnović, Josipa Vlasac; Delić-Brkljačić, Diana

doi:10.1016/j.ajem.2023.05.007

Cited by 6 publications

(3 citation statements)

References 21 publications

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“…28,29 Moreover, remdesivir administration in moderate-severe and critically severe COVID-19 was also associated to better survival when given prior to high-flow oxygen support and to a lower rate of occurrence of arterial thrombotic events. 30,31 In our cohort, we did not observe increased bacterial superinfections nor bradycardia or arterial thrombotic events. We cannot comment on the positive outcome on patient survival of remdesivir administration during low-flow oxygen support as the whole cohort considered in the present study was treated with remdesivir already in a situation of mechanical ventilation.…”

Section: Discussionmentioning

confidence: 44%

Use of canakinumab and remdesivir in moderate-severe COVID-19 patients: A retrospective analysis

Mastroianni

Vangeli

Chidichimo

et al. 2023

Int J Immunopathol Pharmacol

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Objectives: The dysregulated immune response occurring upon COVID-19 infection can lead to tissue damage and organ failure. Different therapeutic strategies are needed to cope with the current and future outspread of COVID-19, including antiviral and anti-inflammatory agents. We describe the outcome of hospitalized patients treated with canakinumab and remdesivir plus the standard of care therapy. Methods: This observational study describes the outcome of the combination of canakinumab (450 mg for patients ≥40 and <60 kg, 600 mg for those ≥60 and <80 kg, or 750 mg for patients ≥80 kg) and 200 mg remdesivir intravenous infusion, plus standard of care (SOC), in 17 moderate-to-severe COVID-19 patients hospitalized in the “Annunziata” Hospital, Cosenza, Italy, between August and November 2021. Hematological markers, biochemical, and hemogasanalysis values at baseline versus day 7 of combination treatment were compared by paired t test after checking for normal distribution and correcting for multiple comparison. Results: The median age of patients was 64 years (range: 39–85), and the median hospitalization time (calculated on the 16 patients that were not transferred to intensive care unit) was of 12.5 days (range: 7–35 days); 15/17 patients (88%) did not experience complications. After 7 days of combination therapy, all the inflammatory parameters were significantly reduced with the exception of procalcitonin; moreover, hematological prognostic markers such neutrophil-to-lymphocyte ratio, CRP-to-lymphocyte ratio, and derived neutrophil-to-lymphocyte ratio reduced. Overall, 16/17 patients (94%) recovered after 14 days. Conclusions: Canakinumab and remdesivir treatment, in addition to SOC, in the early stage of moderate-to-severe COVID-19 showed promising outcomes in terms of safety and effectiveness potentially leading to a reduction in inflammatory and hematological prognostic markers after 7 days of treatment.

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Section: Discussionmentioning

confidence: 44%

Use of canakinumab and remdesivir in moderate-severe COVID-19 patients: A retrospective analysis

Mastroianni

Vangeli

Chidichimo

et al. 2023

Int J Immunopathol Pharmacol

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“…On the other hand, ADP metabolite potentiates serotonin-mediated platelet aggregation. Adenosine may also hamper immune response mediated by T cell and reduce inflammation which might suggest rationale for predisposition to observed bacteriemia in RDV users (Galan et al, 2009; Layland et al, 2014; Lucijanic et al, 2022, 2023; Vijayan et al, 2017). It has been shown that a hypoxemic setting in inflammatory bowel disease stimulates serotonin synthesis and release and is potentiated by adenosine agonist (Dammen et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Specific adverse outcomes associated with selective serotonin reuptake inhibitors use in COVID-19 patients might be potentiated by remdesivir use

Papic,

Bistrovic,

Krecak

et al. 2024

J Psychopharmacol

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Background: Due to non-consistent reports in the literature, there are uncertainties about the potential benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in patients with Coronavirus disease 2019 (COVID-19). Aim: To investigate associations of SSRIs with clinical characteristics and unwanted outcomes among real-life severe and critical COVID-19 patients and their relationship with remdesivir (RDV) use. Methods: This retrospective cohort study evaluated a total of 1558 COVID-19 patients of the white race treated in a tertiary center institution, among them 779 patients treated with RDV and 779 1:1 case-matched patients. Results: A total of 78 (5%) patients were exposed to SSRIs during hospitalization, similarly distributed among patients treated with RDV and matched patients (5.1 and 4.9%). No significant associations of SSRI use with age, sex, comorbidity burden, and COVID-19 severity were present in either of the two cohorts ( p < 0.05 for all analyses). In multivariate analyses adjusted for clinically meaningful variables, SSRI use was significantly associated with higher mortality among RDV (adjusted odds ratio (aOR) 2.0, p = 0.049) and matched patients (aOR 2.22, p = 0.044) and with higher risk for mechanical-ventilation (aOR 2.57, p = 0.006), venous-thromboembolism (aOR 3.69, p = 0.007), and bacteremia (aOR 2.22, p = 0.049) among RDV treated patients. Conclusions: Adverse outcomes associated with SSRI use in COVID-19 patients might be potentiated by RDV use, and clinically significant interactions between these two drug classes might exist. Although our findings raise important considerations for clinical practice, they are limited by retrospective nature of the study, lack of ethnic diversity, and the potential for unmeasured confounding factors. Future studies exploring underlying biological mechanisms are needed.

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“…These results are in line with previous observations, as remdesivir use might increase the occurrence of BSIs, even among patients treated with lower CS doses. It is unclear whether these observations are confounded by other variables associated with remdesivir use, and intravenous applications of the drug, or may indeed represent a true phenomenon, due to similarities of remdesivir metabolites to adenosine, which is known to attenuate the inflammatory and immune responses [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Corticosteroid Dosing Level, Incidence and Profile of Bacterial Blood Stream Infections in Hospitalized COVID-19 Patients

Papic,

Bistrovic,

Cikara

et al. 2024

Viruses

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COVID-19 patients with severe or critical symptoms are often treated with corticosteroids, per contemporary guidelines. Due to their immunosuppressive and immunomodulatory properties, corticosteroids are associated with the development of superinfections. We aimed to retrospectively assess patterns of corticosteroid use and the profiles of bacterial blood stream infections associated with exposure to different dosing levels, in a cohort of 1558 real-life adult COVID-19 patients. A total of 1391 (89.3%) patients were treated with corticosteroids, with 710 (45.6%) patients receiving low, 539 (34.6%) high and 142 (9.1%) very high corticosteroid doses. Bacteremia developed in a total of 178 (11.4%) patients. The risk of bacteremia was of similar magnitude between the no and low-dose corticosteroid treatments (p = 0.352), whereas it progressively increased with high (OR 6.18, 95% CI (2.66–14.38), p < 0.001) and very high corticosteroid doses (OR 8.12, 95% CI (3.29–20.05), p < 0.001), compared to no corticosteroid treatment. These associations persisted after multivariate adjustments and were present independently of sex, comorbidity burden, and mechanical ventilation. The profiles of individual bacterial pathogens differed depending on the used corticosteroid doses. High and very high corticosteroid doses are frequently used for real-life COVID-19 patients with severe and critical clinical presentations and are associated with a higher risk of bacteremia independently of sex, comorbidity burden, and mechanical ventilation use.

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Remdesivir use in severe and critical COVID-19 patients might be associated with lower incidence of arterial thrombotic events

Cited by 6 publications

References 21 publications

Use of canakinumab and remdesivir in moderate-severe COVID-19 patients: A retrospective analysis

Use of canakinumab and remdesivir in moderate-severe COVID-19 patients: A retrospective analysis

Specific adverse outcomes associated with selective serotonin reuptake inhibitors use in COVID-19 patients might be potentiated by remdesivir use

Corticosteroid Dosing Level, Incidence and Profile of Bacterial Blood Stream Infections in Hospitalized COVID-19 Patients

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