Endothelial, Immunothrombotic, and Inflammatory Biomarkers in the Risk of Mortality in Critically Ill COVID-19 Patients: The Role of Dexamethasone

Keskinidou, Chrysi; Vassiliou, Alice G.; Zacharis, Alexandros; Jahaj, Edison; Gallos, Parisis; Dimopoulou, Ioanna; Orfanos, Stylianos E.; Kotanidou, Anastasia

doi:10.3390/diagnostics11071249

Cited by 21 publications

(61 citation statements)

References 30 publications

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“…Very low quality: we are very uncertain about the estimate. 1 Downgraded for risk of bias and imprecision (95% CI includes line of no effect); 2 downgraded twice for risk of bias; 3 downgraded for risk of bias, imprecision, and inconsistency (due to heterogeneity); 4 downgraded for risk of bias and inconsistency; 5 downgraded for risk of bias, inconsistency, and indirectness.…”

Section: High-risk Population (Severe Disease)mentioning

confidence: 99%

See 1 more Smart Citation

Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis

Cruciani¹,

Pati²,

Masiello³

et al. 2021

Diagnostics

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Background. Ivermectin has received particular attention as a potential treatment for COVID-19. However, the evidence to support its clinical efficacy is controversial. Objectives. We undertook a new systematic review of ivermectin for the treatment and prophylaxis of COVID-19, including new primary studies, outcomes other than mortality, and grading the quality of the available evidence following the Cochrane guidance for methodology. Methods. We searched electronic databases, repository databases, and clinical trial registries (up to June 2021). The measure of treatment effect was risk difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the evidence. Results. The review includes 11 RCTs (2436 participants). The certainty of the available evidence was quite low or very low due to risk of bias, inconsistency, and imprecision. When the analysis was limited to patients with baseline mild or moderate disease (8 reports, 1283 patients), there were no differences in mortality between ivermectin and control groups (low level of certainty); in patients with baseline severe diseases (3 reports, 304 patients), the use of ivermectin significantly decreased mortality compared to the controls (RD −0.17; 95% CIs, −0.24/−0.10; p = 0.00001; low level of certainty). In terms of disease progression (to severe pneumonia, admission to intensive care unit, and/or mechanical ventilation), the results were much the same. At day 14, the rate of patients with a negative RT-PCR test was 21% higher (from 5 to 36% higher) for ivermectin recipients than it was for the controls (low quality of evidence). Three studies (736 subjects) indicated that prophylaxis with ivermectin increased the likelihood of preventing COVID-19 compared to controls (low quality of evidence). Serious adverse events were rarely reported. Conclusions. There is limited evidence for the benefit of ivermectin for COVID-19 treatment and prophylaxis, and most of this evidence is of low quality. Further evidence is needed to fine-tune potential indications and optimal treatment protocols for ivermectin as a treatment for COVID-19.

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Section: High-risk Population (Severe Disease)mentioning

confidence: 99%

“…Several drugs have been considered for the treatment of SARS-CoV-2, and various unconventional treatments have been hailed as potential cures for COVID-19 [ 1 , 2 , 3 , 4 ]. One of the latest putative silver bullets against COVID-19 is ivermectin [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis

Cruciani¹,

Pati²,

Masiello³

et al. 2021

Diagnostics

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“…Certain blood-based biomarkers, such as lymphocyte, neutrophil and platelet counts, neutrophil-tomonocyte ratio (NMR), neutrophil-to-lymphocyte ratio (NLR), D-dimer, interleukin-6, C-reactive protein (CRP) levels and lactate dehydrogenase (LDH) may discriminate between severe and non-severe COVID-19 (4,7,8). Another biomarker, the soluble urokinase plasminogen activator receptor (suPAR), has been shown to be significantly elevated in patients with COVID-19 (9), and stands out as a predictor of overall disease severity and outcome (10)(11)(12)(13)(14)(15) and in particular of severe respiratory failure (16), and acute kidney injury (17) due to SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19

et al. 2021

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Background: Efficient healthcare based on prognostic variables in hospitalised patients with COVID-19 could reduce the risk of complications and death. Recently, soluble urokinase Plasminogen Activator Receptor (suPAR) was shown to predict respiratory failure, kidney injury, and clinical outcome in patients with SARS-CoV-2 infection. The aim of this study was to investigate the value of suPAR as a prognostic tool, in comparison with other variables, regarding disease severity and length of hospital stay in patients with COVID-19.Patients and Methods: Individuals hospitalised with COVID-19 (40 males, 20 females; median age 57.5 years) with a median symptom duration of 10 days and matched, healthy controls (n = 30) were included. Admission levels of suPAR were measured in serum by enzyme-linked immunosorbent assay. Blood cell counts, C-reactive protein (CRP) levels, lactate dehydrogenase (LDH), plasma creatinine and estimated glomerular filtration rates were analysed and oxygen demand, level of care and length of hospitalisation recorded.Results: Patients had significantly higher suPAR levels compared to controls (P < 0.001). Levels were higher in severely/critically (median 6.6 ng/mL) compared with moderately ill patients (median 5.0 ng/mL; P = 0.002). In addition, suPAR levels correlated with length of hospitalisation (rho = 0.35; P = 0.006). Besides suPAR, LDH, CRP, neutrophil count, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratio, body mass index and chronic renal failure were discriminators of COVID-19 severity and/or predictors of length of hospitalisation.Conclusion: Admission levels of suPAR were higher in patients who developed severe/critical COVID-19 and associated with length of hospital stay. In addition, we showed that suPAR functioned as an independent predictor of COVID-19 disease severity.

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“…16,17 The clinical benefits noted with the use of Tocilizumab and Dexamethasone were attributed to the immunomodulation at the level of the endothelium. 18,19 Byttebier et. al demonstrated in a retrospective study that the concurrent treatment with statins, aspirin, and ACE/ARBs, which have protective effects on the endothelium, resulted in a 3-fold reduction in the odds of hospital mortality.…”

Section: Discussionmentioning

confidence: 99%

“…The coronavirus disease 2019 (COVID- 19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a global challenge worldwide. Although considered at its emergence as a respiratory infection, recent studies demonstrated tropism towards endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Managing Endothelial Dysfunction in COVID-19: A Pilot, Double-Blind, Placebo-Controlled, Randomized Clinical Trial at the Lebanese American University Medical Center - Rizk Hospital (MEDIC-LAUMCRH)

Matli

Kotob

Jamaleddine

et al. 2022

Preprint

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Background: Coronavirus disease 2019 (Covid-19) is associated with endothelial dysfunction. Pharmacologically targeting the different mechanisms of endothelial dysfunction may improve clinical outcomes and lead to reduced morbidity and mortality Methods: In this pilot, double-blind, placebo-controlled, randomized clinical trial we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID-19 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L-arginine, Folate, Nebivolol, and Atorvastatin) or placebo for up to 14 days. The primary outcome was time to recovery, measured by an 8 category ordinal scale and defined by the time to being discharged from the hospital or hospitalized for infection-control or other nonmedical reasons. Secondary outcomes included the composite outcome of ICU admission or the need for mechanical ventilation, all-cause mortality, and the occurrence of side effects Results: Of 42 randomized patients, 37 were included in the primary analysis. The mean age of the patients was 57 years; the mean BMI of study participants was 29.14. History of hypertension was present in 27% of the patients, obesity in 45%, and Diabetes Mellitus in 21.6%. The median(Interquartile range) time to recovery was not significantly different between the endothelial protocol group (6 [4-12] days) and the placebo group (6 [5-8]days)(p-value = 0.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all-cause mortality, and the occurrence of side effects between the endothelial protocol group and the placebo group. Conclusion: Among patients hospitalized with mild, moderate, or severe COVID-19 infection, targeting endothelial dysfunction by administering Nicorandil, L-arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. However, this treatment protocol was associated with an excellent safety profile. Adequately sized prospective randomized controlled trials are needed for the evaluation of the role of treating endothelial dysfunction in COVID-19 infection.

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Endothelial, Immunothrombotic, and Inflammatory Biomarkers in the Risk of Mortality in Critically Ill COVID-19 Patients: The Role of Dexamethasone

Cited by 21 publications

References 30 publications

Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis

Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19

Managing Endothelial Dysfunction in COVID-19: A Pilot, Double-Blind, Placebo-Controlled, Randomized Clinical Trial at the Lebanese American University Medical Center - Rizk Hospital (MEDIC-LAUMCRH)

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