Dissertation committee:
Ορφανός Στυλιανός, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Λάγιου Παγώνα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κοτανίδου Αναστασία, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Δημοπούλου Ιωάννα-Μαρία, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Βασιλειάδης Ιωάννης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κατσαούνου Παρασκευή, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Σιέμπος Ηλίας, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Introduction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the infectious cause of coronavirus disease 19 (COVID-19), which was declared a pandemic by the World Health Organization (WHO) in March 2020. COVID-19 is characterized by a plethora of clinical manifestations and variable disease severity. Patients who develop critical illness are admitted to the intensive care unit (ICU). Endothelial dysfunction, immunothrombosis, and inflammation seem to play an important role in the pathogenesis of SARS-CoV-2, and there could be a possible connection between the abovementioned events and the disease severity of hospitalized COVID-19 patients.
Objective. The aim of this doctoral thesis was to evaluate the role of endothelium-related molecules, which have been previously investigated as potential biomarkers for the early diagnosis and/or prognosis of sepsis and acute respiratory distress syndrome (ARDS), in the prognosis of poor clinical outcomes in the context of COVID-19.
Methodology. We measured the soluble levels of 23 biomarkers that denote endothelial activation/dysregulation in critically-ill and hospitalized COVID-19 patients, as well as SARS-CoV-2 positive outpatients. Sampling occurred within the first 24 h post ICU or hospital admission or upon hospital visit. Soluble levels of the selected biomarkers were measured in serum or plasma samples by enzyme-linked immunosorbent assay (ELISA).
Results. From a total of 124 COVID-19 recruited in the study, 37 were critically-ill patients from the “first wave”, who did not receive dexamethasone as part of their treatment regime. Our results indicated that in our cohort, ICU admission levels of soluble E-selectin, sP-selectin, angiopoietin 2, sICAM-1, vWf, TREM-1, presepsin, ΤΜΕΜ173, plasminogen, sVCAM-1, suPAR, and EphA2 were higher in COVID-19 critically-ill patients who did not survive. Moreover, E-selectin, angiopoietin 2, sICAM-1, sVCAM-1, and suPAR exhibited good discriminating ability in predicting ICU mortality. Also, in the study we included 29 critically-ill COVID-19 patients who had received the first dose (6mg) of dexamethasone prior to sampling. We observed that the administration of dexamethasone reduced the levels of several biomarkers. However, sVCAM-1, presepsin, and suPAR could still differentiate patients who did not survive their illness, independently of dexamethasone administration. Finally, plasma sEPCR levels were measured on hospital admission in 84 COVID-19 patients and in 11 non-hospitalized SARS-CoV2-positive patients. In our cohort, sEPCR levels in COVID-19 patients upon hospital admission appeared considerably elevated compared with outpatients. Additionally, sEPCR combined with BMI, age, or D-dimers showed a high prediction ability for hospitalization.
Conclusions. Our results indicated that there is a connection between inflammatory activation and endothelial dysfunction in the manifestation of COVID-19. Many of the selected endothelial biomarkers could differentiate patients who did not survive their illness, independently of dexamethasone administration (measured after the first dose of 6mg), and could also provide important clinical information. A complete understanding of the mechanisms involved in the activation of the secretion of the above endothelial biomarkers could help in patient stratification and risk assessment for each individual patient.
Keywords:
COVID-19, Endotheliopathy, Immunothrombosis, Inflammation, ICU
