Βιοδείκτες στη θεραπευτική της νόσου Covid-19

Η παρούσα διπλωματική εργασία εξετάζει την εφαρμογή των βιοδεικτών στην θεραπεία της νόσου Covid-19. Στο γενικό μέρος γίνεται μια βιβλιογραφική ανασκόπηση των 11 μελετών που έχουν σχέση με τους βιοδείκτες αυτούς. Στην αρχή μελετήθηκε η διαφορετική γονιδιακή έκφραση και η επίδραση ορισμένων γονιδίων όπως το TLR6, το MMP9, το SCAP1 και το LAG3 στα διαφορετικά στάδια της νόσου. Ακολούθως, γίνεται περιγραφή της τροποποίησης των Β-κυττάρων από τη νόσο Covid-19 και την υπεροχή ορισμένων υποομάδων τους ανάλογα με τη σοβαρότητα της νόσου. Στη συνέχεια, μελετήθηκε πως η ενεργοποίηση του φλεγμονοσώματος NLRP3 μπορεί να χρησιμοποιηθεί ως βιοδείκτης της εξέλιξης της νόσου Covid-19. Κατόπιν, σημαντική είναι και η μελέτη της συμπεριφοράς των ιντερφερονών IFN-α και IFN-β στα σοβαρά στάδια της νόσου, αλλά και στη βελτίωσή της. Η μελέτη εφαρμογής της TPE ως θεραπεία στη Covid-19, στα σοβαρά στάδια της νόσο κρίνεται σημαντική. Ο βιοδείκτης IL-6 περιγράφεται στην αντίστοιχη μελέτη ως βιοδείκτης πρόγνωσης νόσου, αλλά και ως στόχος θεραπείας από την τοσιλιζουμάμπη, ανταγωνιστή του υποδοχέα της IL-6 που χρησιμοποιείται σε ασθενείς με σοβαρή νόσο. Σημαντικοί επίσης είναι οι βιοδείκτες ενδοθηλιακής βλάβης, όπως SVCAM1 και η θρομβομοδουλίνη, διότι στη νόσο Covid-19 κυριαρχεί αυτή η ενδοθηλιακή βλάβη κυρίως στον πνεύμονα. Η χρήση του HBP ως βιοδείκτης βαρύτητας νόσου εξετάζεται κυρίως σε ασθενείς με Covid-19 που ανέπτυξαν οργανική ανεπάρκεια. Τέλος, ο ανοσολογικός βιοδείκτης suPAR μελετήθηκε ως πρώιμος δείκτης φλεγμονής σε τιμές ≥ 6 ng/ml σε ασθενείς με ήπια ή μέτρια νόσο Covid-19, ώστε να εφαρμοστεί η θεραπεία με ανακίνρα. Στο ειδικό μέρος γίνεται αναφορά στη μελέτη SAVE, η οποία χρησιμοποιεί τον βιοδείκτη suPAR, ώστε να μελετηθούν τα αποτελέσματα της θεραπείας με ανακίνρα που αποτελεί τον ανταγωνιστή του υποδοχέα IL-1 στην εξέλιξη της νόσου σε σοβαρή αναπνευστική ανεπάρκεια. Συγκρίθηκαν τα αποτελέσματα της θεραπείας με ανακίνρα σε ασθενείς με ίδιο στάδιο νόσου οι οποίοι έλαβαν μόνο την SOC θεραπεία. Επίσης, γίνεται αναφορά στην κατάλληλη χρονική στιγμή που πρέπει να εφαρμοστεί η θεραπεία με ανακίνρα στην πορεία της νόσου, ώστε να έχουμε τα καλύτερα δυνατά αποτελέσματα.The present diploma thesis examines the application of biomarkers in the treatment of Covid-19 disease. In the general part there is a literature review of the 11 studies related to these biomarkers. At the beginning, the different gene expression, and the effect of certain genes such as TLR6, MMP9, SCAP1 and LAG3 were studied at different stages of the disease. Next, a description is made of the modification of B-cells by Covid-19 disease and the predominance of some of their subgroups depending on the severity of the disease. Then, important is the study of the behavior of interferons IFN-α and IFN-β in the severe stages of the disease, but also in its improvement. Described in the respective study as a biomarker of disease prognosis, but also as a target of treatment with tocilizumab, an antagonist of the IL-6 receptor used in patients with severe disease. HBP as a disease severity biomarker is mainly tested in patients with Covid-19 who developed organ failure. Finally, the suPAR was studied as an early biomarker of Inflammation at values of ≥ 6 ng / ml in patients with mild or moderate Covid-19 disease, to apply the treatment with anakinra. In the specific part, reference is made to the SAVE trial, which uses the suPAR biomarker, to study the effects of anakinra therapy that is the inhibitor of IL-1 on the progression of the disease to severe respiratory failure. The results of treatment with anakinra were compared in patients with the same disease stage who received only the SOC treatment therapy. Also, reference is made to the appropriate time when the treatment with anakinra should be applied in the course of the disease, to have the best possible results

Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model

IntroductionPost-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD).MethodsIn this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1.ResultsTwo hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and <60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and <60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and <5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5–29% and <5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic.ConclusionPost-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are “immature.” Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches

Infliximab-Induced Erythema Multiforme in a Patient with Chronic Sarcoidosis

Tumor Necrosis Factor-α (TNF-α) inhibitors, in particular infliximab, have shown effectiveness as a third-line treatment option in relapsing, refractory sarcoidosis that requires an increased dose of corticosteroids plus one or more anti-sarcoidosis disease modifying drugs [...

Predictors of Mortality in Tocilizumab-Treated Severe COVID-19

Purpose: Tocilizumab is associated with positive outcomes in severe COVID-19. We wanted to describe the characteristics of nonresponders to treatment. Methods: This was a retrospective multicenter study in two respiratory departments investigating adverse outcomes at 90 days from diagnosis in subjects treated with tocilizumab (8 mg/kg intravenously single dose) for severe progressive COVID-19. Results: Of 121 subjects, 62% were males, and 9% were fully vaccinated. Ninety-six (79.4%) survived, and 25 died (20.6%). Compared to survivors (S), nonsurvivors (NS) were older (median 57 versus 75 years of age), had more comorbidities (Charlson comorbidity index 2 versus 5) and had higher rates of intubation/mechanical ventilation (p 2/FiO2 ratio, higher blood ferritin, and higher troponin, and on clinical progression (day of tocilizumab treatment), NS had a lower PO2/FiO2 ratio, decreased lymphocytes, increased neutrophil to lymphocyte ratio, increased ferritin and lactate dehydrogenase (LDH), disease located centrally on computed tomography scan, and increased late c-reactive protein. Cox proportional hazards regression analysis identified age and LDH on deterioration as predictors of death; admission PO2/FiO2 ratio and LDH as predictors of intubation; PO2/FiO2 ratios, LDH, and central lung disease on radiology as predictors of noninvasive ventilation (NIV) (a p < 0.001). ROC analysis of the above predictors in a separate validation cohort yielded significant results. Conclusions: Older age and high serum LDH levels are predictors of mortality in tocilizumab-treated severe COVID-19 patients. Hypoxia levels, LDH, and central pulmonary involvement radiologically are associated with intubation and NIV