Elevated inflammatory markers are associated with poor outcomes in COVID‐19 patients treated with remdesivir

Stoeckle, Kate; Witting, Britta; Kapadia, Shashi N; An, Anjile; Marks, Kristen

doi:10.1002/jmv.27280

Cited by 16 publications

(12 citation statements)

References 17 publications

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“…13 Recent reports have shown that some patients with the severe form of the Covid-19 infection experience an intensified immune response similar to cytokine release syndrome and multisystem inflammatory syndrome. 14 Consistent with us, a prior study by Stoeckle et al 15 have shown that CRP levels decrease significantly after remdesivir therapy in none intubated Covid-19 patients, indicating that remdesivir mitigates inflammatory response in a certain group of patients but not in all. Moreover, women patients in the study had lower CRP levels than men that may be due to the lower viral load level, higher number of CD 4+ T cells, and higher levels of antibodies in women.…”

Section: Discussionsupporting

confidence: 84%

Linear mixed model analysis to evaluate correlations between remdesivir adverse effects with age and gender of patients with mild Covid‐19 pneumonia

Sedighi

Amanollahi

Moghaddam

et al. 2022

Journal of Medical Virology

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We aimed to assess longitudinal changes in clinical indexes of corona disease 2019 patients with mild pulmonary infection during 5 days of remdesivir therapy and determine the effect of age and gender on remdesivir adverse effects (AE). Patients' clinical data including inflammatory markers, liver and renal function tests, and heart rate (HR) were extracted from medical records. Linear mixed model (LMM) was used to analyze longitudinal changes in patients' clinical indexes. Gender and age were inserted in LMM as covariates to find their correlation with AE and clinical indexes. Of 84 patients, 35 patients met our criteria for the study. There were significant increases in mean levels of white blood cell (WBC; p = 0.005), alanine aminotransferase (ALT; p = 0.001), aspartate aminotransferase (p = 0.001), blood urea nitrogen (BUN; p = 0.001), and creatinine (p = 0.006), whereas mean levels of erythrocyte sedimentation rate (p = 0.005), C-reactive protein (p = 0.001), alkaline phosphatase (p = 0.001), and potassium (p = 0.003) decreased significantly. Estimated glomerular filtration rate (p = 0.001) and HR (p = 0.001) showed a notable decline over the course of treatment. LMM analysis showed that mean changes in WBC (β = 0.94, p = 0.029), creatinine (β = 0.12, p = 0.020), and HR (β = 6.47, p = 0.008) were greater in males than in females. Also, age of patients had a significant effect on the mean changes of WBC (β = −0.02, p = 0.023), sodium (β = −0.06, p = 0.010), BUN (β = 0.23, p = 0.001), and HR (β = −0.29, p = 0.001). Despite no renal and liver dysfunction, Covid-19 patients with mild pulmonary infection may develop some remdesivir AE and attributed side effects might be affected by gender and age of patients.

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Section: Discussionsupporting

confidence: 84%

Linear mixed model analysis to evaluate correlations between remdesivir adverse effects with age and gender of patients with mild Covid‐19 pneumonia

Sedighi

Amanollahi

Moghaddam

et al. 2022

Journal of Medical Virology

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“…Signi cant reduction in CRP levels and in ammatory cytokines levels were seen in remdesivir treated group patients indicating the immunomodulatory and anti-in ammatory role of remdesivir as well as corticosteroids therapy [25][26]. Also, these ndings are consistent with the study by Kate Stoeckle et al which shows CRP levels decreased signi cantly after remdesivir administration in patients who remained non-intubated over the study period [27]. The decrease in CRP levels after corticosteroids administration has also been well documented in the literature.…”

Section: Discussionsupporting

confidence: 87%

Evaluation of Clinical Outcomes After Remdesivir Therapy in Patients with Moderately Severe Covid-19 Disease. Prospective Study

Liaqat

Zafar

Asad

et al. 2022

Preprint

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Background Despite the fact that a number of therapeutic agents have been tested for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been proven to be effective. Objectives This study aims to evaluate the favorable clinical outcomes after remdesivir treatment in hospitalized patients with moderately severe COVID-19 disease in Pakistan. Methods A prospective study in hospitalized patients with moderately severe Covid-19 disease was conducted between January 2021- October 2021. The patients were divided into remdesivir-treated and control groups. The Remdesivir-treated group received 200mg IV, followed by 100mg once daily for four days. In addition to standard care, all patients received corticosteroid therapy. The clinical status of remdesivir patients was assessed after the 5th day of treatment, including proportion negative polymerase chain reaction test for COVID-19, length of hospitalization, improvement in oxygen demand, and effects on C-reactive protein (CRP) levels. Multivariate analysis and paired sample T-test were performed to evaluate a favorable response to remdesivir treatment and results were compared with a control group. Result In total, 328 patients were enrolled in the study, with 162 of them receiving IV remdesivir on the day of admission. The C-reactive protein level in the remdesivir treated group [median 22.0 (14.0–36.7)] was significantly lower (p < 0.001) than in the remdesivir naive group [median 79.1 (57.4–139.0)]. The number of days spent in the hospital was significantly different between the remdesivir-treated and remdesivir-naive groups [6.2 0.5] (p < 0.001). In the remdesivir-treated group, 36.7% of patients were discharged with a negative PCR, compared to 21.6% in the control group (p < 0.001). In comparison to the control group, the remdesivir treated group showed a significant improvement in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (p < 0.001). Conclusion The remdesivir treatment was found to be superior to improve clinical outcomes among moderately severe Covid-19 disease patients.

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“…Some authors demonstrated that systemic inflammation can modify drug plasma metabolism. 23 , 24 Therefore, the inflammatory profile related to SARS-CoV-2 infection could influence the remdesivir PK in COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Interpatient variability in the pharmacokinetics of remdesivir and its main metabolite GS-441524 in treated COVID-19 subjects

Tempestilli

Bartoli

Benvenuto

et al. 2022

Journal of Antimicrobial Chemotherapy

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Background Remdesivir is the first antiviral drug against SARS-CoV-2 approved for use in COVID-19 patients. Objectives To study the pharmacokinetic inter-individual variability of remdesivir and its main metabolite GS-441524 in a real-world setting of COVID-19 inpatients and to identify possible associations with different demographic/biochemical variables. Methods Inpatients affected by SARS-CoV-2 infections, undergoing standard-dose remdesivir treatment, were prospectively enrolled. Blood samples were collected on day 4, immediately after (C0) and at 1 h (C1) and 24 h (C24) after infusion. Remdesivir and GS-441524 concentrations were measured using a validated UHPLC-MS/MS method and the AUC0–24 was calculated. At baseline, COVID-19 severity (ICU or no ICU), sex, age, BMI and renal and liver functions were assessed. Transaminases and estimated glomerular filtration rate (e-GFR) were also evaluated during treatment. Linear regression, logistic regression and multiple linear regression tests were used for statistical comparisons of pharmacokinetic parameters and variables. Results Eighty-five patients were included. The mean (CV%) values of remdesivir were: C0 2091 (99.1%) ng/mL, C1 139.7 (272.4%) ng/mL and AUC0–24 2791 (175.7%) ng·h/mL. The mean (CV%) values of GS-441524 were: C0 90.2 (49.5%) ng/mL, C1 104.9 (46.6%) ng/mL, C24 58.4 (66.9) ng/mL and AUC0–24 1976 (52.6%) ng·h/mL. The multiple regression analysis showed that age (P < 0.05) and e-GFR (P < 0.01) were independent predictors of GS-441524 plasma exposure. Conclusions Our results showed a high interpatient variability of remdesivir and GS-441524 likely due to both age and renal function in COVID-19 inpatients. Further research is required to understand whether the pharmacokinetics of remdesivir and its metabolites may influence drug-related efficacy or toxic effect.

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Elevated inflammatory markers are associated with poor outcomes in COVID‐19 patients treated with remdesivir

Cited by 16 publications

References 17 publications

Linear mixed model analysis to evaluate correlations between remdesivir adverse effects with age and gender of patients with mild Covid‐19 pneumonia

Linear mixed model analysis to evaluate correlations between remdesivir adverse effects with age and gender of patients with mild Covid‐19 pneumonia

Evaluation of Clinical Outcomes After Remdesivir Therapy in Patients with Moderately Severe Covid-19 Disease. Prospective Study

Interpatient variability in the pharmacokinetics of remdesivir and its main metabolite GS-441524 in treated COVID-19 subjects

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