IMPACT of PCSK9 inhibition on clinical outcome in patients during the inflammatory stage of the SARS-COV-2 infection: Rationale and protocol of the IMPACT-SIRIO 5 study

Kubica, Jacek; Podhajski, Przemysław; Magielski, Przemysław; Kubica, Aldona; Adamski, Piotr; Junik, Roman; Pinkas, Jarosław; Navarese, Eliano Pio

doi:10.5603/cj.a2021.0148

Cited by 11 publications

(8 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An upcoming study may shed more light on the importance of PCSK9 and associated molecular pathways in patients at risk for acute lung injury: IMPACT-SIRIO 5 study (NCT04941105). The IMPACT-SIRIO 5 is a randomized, double-blind, phase III clinical trial evaluating the safety and efficacy of PCSK9 inhibition on clinical outcome (need for intubation, death of any cause, and changes in IL-6 concentrations) in patients during the acute inflammatory stage of COVID-19 ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Plasma Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in the Acute Respiratory Distress Syndrome

et al. 2022

View full text Add to dashboard Cite

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is a mediator of the immune response to sepsis. PCSK9 is also highly expressed in pneumocytes and pulmonary endothelial cells. We hypothesized that serum PCSK9 levels would be associated with death and ICU outcomes in patients with ARDS.MethodsUsing data and plasma samples from the NIH BioLINCC data repository, we assembled a cohort of 1,577 patients with the acute respiratory distress syndrome (ARDS) enrolled in two previously completed clinical trials, EDEN and SAILS. We measured PCSK9 levels in plasma within 24 h of intubation using commercially available ELISA kits (R&D Systems). We assessed the association of PCSK9 with mortality using Cox proportional hazard models. We also assessed clinical factors associated with PCSK9 level and the association of PCSK9 with the number of days free of mechanical ventilation and days free of ICU care.ResultsIn 1,577 ARDS patients, median age was 53 years (IQR 42–65 years) and median APACHE III score 91 (72–111) connoting moderate critical illness. PCSK9 levels were 339.3 ng/mL (IQR 248.0–481.0). In multivariable models, race, cause of ARDS, body mass index, pre-existing liver disease, body temperature, sodium, white blood cell count and platelet count were associated with PCSK9 level. Presence of sepsis, use of vasopressors and ventilator parameters were not associated with PCSK9 level. PCSK9 levels were not associated with in-hospital mortality (HR per IQR 0.96, 95% CI 0.84–1.08, P = 0.47). Higher PCSK9 levels were associated with fewer ICU and ventilator free days.ConclusionsPlasma PCSK9 is not associated with mortality in ARDS, however higher PCSK9 levels are associated with secondary outcomes of fewer ICU free and ventilator free days. Clinical factors associated with PCSK9 in ARDS are largely unmodifiable. Further research to define the mechanism of this association is warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in the Acute Respiratory Distress Syndrome

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In hypoxic microenvironments, upregulation of PCSK9 induced by dengue virus reduces LDLR-mediated uptake of LDL cholesterol and augments virus infection by promoting de novo cholesterol synthesis in the endoplasmic reticulum, which inhibits STING-mediated antiviral response ( 39 ). Considering its inhibition of STING-mediated antiviral response, PCSK9 might be a potential target for the treatment of COVID-19 ( 40 ), in addition to being a known therapeutic target for hypercholesterolemia ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Serum Proteome Characterization of COVID-19 Patients With Different Severities Revealed Potential Therapeutic Strategies

Zhang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

The COVID-19 pandemic caused by SARS-CoV-2 is exerting huge pressure on global healthcare. Understanding of the molecular pathophysiological alterations in COVID-19 patients with different severities during disease is important for effective treatment. In this study, we performed proteomic profiling of 181 serum samples collected at multiple time points from 79 COVID-19 patients with different severity levels (asymptomatic, mild, moderate, and severe/critical) and 27 serum samples from non-COVID-19 control individuals. Dysregulation of immune response and metabolic reprogramming was found in severe/critical COVID-19 patients compared with non-severe/critical patients, whereas asymptomatic patients presented an effective immune response compared with symptomatic COVID-19 patients. Interestingly, the moderate COVID-19 patients were mainly grouped into two distinct clusters using hierarchical cluster analysis, which demonstrates the molecular pathophysiological heterogeneity in COVID-19 patients. Analysis of protein-level alterations during disease progression revealed that proteins involved in complement activation, the coagulation cascade and cholesterol metabolism were restored at the convalescence stage, but the levels of some proteins, such as anti-angiogenesis protein PLGLB1, would not recovered. The higher serum level of PLGLB1 in COVID-19 patients than in control groups was further confirmed by parallel reaction monitoring (PRM). These findings expand our understanding of the pathogenesis and progression of COVID-19 and provide insight into the discovery of potential therapeutic targets and serum biomarkers worth further validation.

show abstract

“…In late 2019 a highly pathogenic novel coronavirus of severe acute respiratory syndrome (SARS-CoV-2) emerged, causing a global pandemic of coronavirus disease-2019 . This new hitherto unknown disease, has had a huge devastating impact on the lives of individuals and entire societies [1][2][3][4][5][6][7][8][9][10][11][12]. There are three stages of the COVID-19:…”

Section: Introductionmentioning

confidence: 99%

Post-COVID-19 rehabilitation (PCR-SIRIO 8) study. A rationale and protocol of the study

Kubica

Michalski

Pietrzykowski

et al. 2022

Medical Research Journal

View full text Add to dashboard Cite

A substantial proportion of the COVID-19 survivors require the physical and mental support due to the post COVID-19 syndrome. In response to this demand a comprehensive rehabilitation program tailored to the individual needs has been developed. The program is linked with a Post-COVID-19 Rehabilitation (PCR-SIRIO 8) study that aims to objectively evaluate the outcomes of the post-COVID-19 rehabilitation. The study was designed as a prospective, single-center, observational study involving patients suffering from post-COVID-19 syndrome. Patients meeting the inclusion criteria are invited for an initial visit including medical and physiotherapeutic examination. Rehabilitation program includes physical training, therapeutic education, and psychotherapeutic workshops. Individual psychotherapeutic, educational and medical visits are carried out additionally depending on the patient's needs. Closing visit evaluates individual effects of the rehabilitation program.We believe that our observational study will provide knowledge necessary to optimize post-COVID-19 rehabilitation.

show abstract

IMPACT of PCSK9 inhibition on clinical outcome in patients during the inflammatory stage of the SARS-COV-2 infection: Rationale and protocol of the IMPACT-SIRIO 5 study

Cited by 11 publications

References 62 publications

Plasma Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in the Acute Respiratory Distress Syndrome

Plasma Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in the Acute Respiratory Distress Syndrome

Longitudinal Serum Proteome Characterization of COVID-19 Patients With Different Severities Revealed Potential Therapeutic Strategies

Post-COVID-19 rehabilitation (PCR-SIRIO 8) study. A rationale and protocol of the study

Contact Info

Product

Resources

About