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Significance assessment of serum amyloid A and other acute phase reactants during SARS-CoV-2 infection for severity of the clinical presentation, hospitalization, and death

dc.contributor.advisorŠipetić-Grujičić, Sandra
dc.contributor.otherIgnjatović, Svetlana
dc.contributor.otherMaksimović, Jadranka
dc.contributor.otherStevanović, Goran
dc.contributor.otherBećarević, Mirjana
dc.creatorJegorović, Boris
dc.date.accessioned2023-11-04T12:14:40Z
dc.date.available2023-11-04T12:14:40Z
dc.date.issued2023-09-22
dc.identifier.urihttps://uvidok.rcub.bg.ac.rs/doccall/bitstream/handle/123456789/5424/Referat.pdf
dc.identifier.urihttps://eteze.bg.ac.rs/application/showtheses?thesesId=9295
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:31448/bdef:Content/download
dc.identifier.urihttps://plus.cobiss.net/cobiss/sr/sr/bib/127349257
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/21847
dc.description.abstractKrajem decembra 2019. godine u Kini je otkriven novi koronavirus, nazvan teški akutni respiratorni sindrom koronavirus 2 (eng. Severe Acute Respiratory Syndrome Coronavirus-2 [SARS- CoV-2]), za koji je pokazano da je uzrok slučajeva pneumonije nepoznate etiologije koji su se javili početkom istog meseca. Ova nova bolest je nazvana Koronavirusna bolest 2019 (eng. Coronavirus Disease 2019 [COVID-19]). Tri meseca kasnije je postala globalni problem kada je Svetska zdravstvena organizacija proglasila pandemiju ove bolesti. Bolest može imati različite kliničke manifestacije, a može dovesti i do nastanka različitih komplikacija i smrtnog ishoda. Uvidevši da je COVID-19 nepredvidiv, postalo je od suštinskog značaja otkriti pouzdane kliničko-laboratorijske markere za svakodnevnu upotrebu radi procene težine bolesti i potencijalno nepovoljnih ishoda. Cilj ovog istraživanja je procena značaja određivanja serumskog amiloida A (SAA), drugih reaktanata akutne faze (RAF) i ostalih inflamatornih parametara kod ambulantnih pacijenata sa SARS-CoV-2 infekcijom, kao i identifikacija povezanosti između ovih laboratorijskih markera sa jedne strane, i težine i ishoda bolesti sa druge. Materijal i metode: Ovom prospektivnom kohortnom studijom obuhvaćeni su pacijenti koji su u periodu od avgusta do novembra 2020. godine pregledani u Prijemnoj ambulanti Klinike za infektivne i tropske bolesti „Prof. dr Kosta Todorović“ u Beogradu i kod kojih je dokazan COVID- 19. Na osnovu kliničkih kriterijuma sastavljenih od strane Svetske zdravstvene organizacije pacijenti su bili klasifikovani prema težini bolesti na ispitanike sa blagom, umereno teškom i teškom bolešću. Od ispitanika su prikupljeni demografski podaci, podaci o komorbiditetima, simptomima i znacima SARS-CoV-2 infekcije. Kod svakog ispitanika je urađen fizikalni pregled sa merenjem vitalnih parametara i radiografija pluća, na osnovu kojih su pacijenti svrstavani u različite grupe težine bolesti (blagi, srednje teški i teški oblik bolesti) prema kriterijumima Svetske zdravstvene organizacije. U uzorcima periferne krvi merene su vrednosti SAA, C-reaktivnog proteina (CRP), interleukina-6 (IL-6), prokalcitonina (PCT), feritina, fibrinogena, D-dimera, albumina, transferina i gvožđa, kao i drugih inflamatornih parametara. Medijane vrednosti RAF i drugih inflamatornih parametara su poređene između ispitanika sa različitom težinom bolesti, hospitalizovanih i nehospitalizovanih, kao i između preživelih i umrlih. Korišćena je Receiver operator characteristic (ROC) kriva i Area-under-curve (AUC) za analizu klasifikacionih karakteristika pojedinačnih RAF za težinu bolesti, hospitalizaciju i smrtni ishod, dok su univarijantnom i multivarijantnom logističkom regresionom analizom identifikovani nezavisni prediktori teške i srednje teške bolesti, hospitalizacije i smrtnog ishoda. Rezultati: Kod pacijenata sa teškim oblikom bolesti, kao i hospitalizovanih i umrlih bili su prisutni značajno viši nivoi SAA, CRP, IL-6, PCT i značajno niži nivoi transferina, albumina i gvožđa. Kod pacijenata sa teškim oblikom bolesti i hospitalizovanih su takođe primćene značajno više vrednosti nivoa feritina, fibrinogena, brzine sedimentacije eritrocita, neutrofila, kao i niže vrednosti limfocita i eozinofila. ROC analizom, a na osnovu AUC, nivoi SAA su pokazali zadovoljavajuće klasifikacione karakteristike u odnosu na težinu bolesti (0,794) i smrtni ishod (0,732), a za hospitalizaciju dobre klasifikacione karakteristike (0,853). Multivarijantna logistička regresiona analiza je pokazala da je uzrast značajan nezavistan prediktor srednje teškog i teškog oblika COVID- 19, hospitalizacije i smrtnog ishoda, kako među svim ispitanicima, tako i po polu. Kod svih ispitanika vrednost SAA je identifikovana kao značajan nezavistan prediktor srednje teškog i teškog oblika COVID-19 i hospitalizacije, a kod osoba muškog i ženskog pola samo za teški oblik COVID- 19 i hospitalizaciju. Za smrtni ishod, značajni nezavisni prediktori su uzrast, nivo albumina i broj trombocita. Zaključak: Određivanje nivoa SAA, drugih RAF i ostalih inflamatornih parametara kod ambulantnih pacijenata sa SARS-CoV-2 infekcijom može biti od velikog značaja za procenu težine i prognoze COVID-19.sr
dc.description.abstractIntroduction: In December 2019, a new coronavirus was discovered in China. Named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), it was found that this virus is the cause of cases of pneumonia of previously unknown etiology that had occurred at the beginning of the same month. The disease was named Coronavirus Disease 2019 (COVID-19). Three months later, COVID- 19 became a global problem when the World Health Organization declared a pandemic. The disease can have various clinical manifestations and can also lead to the development of different complications and death. Recognizing that COVID-19 is unpredictable, it has become essential to identify reliable clinical and laboratory markers in everyday practice for disease severity assessment and for the detection of potentially unfavorable outcomes. This study aims to evaluate the significance of determining serum amyloid A (SAA), other acute phase reactants (APRs), and other inflammatory parameters in ambulatory care patients with SARS-CoV-2 infection, as well as to identify the correlation between these laboratory markers on the one hand, and disease severity and outcome on the other. Material and methods: This prospective cohort study included patients examined at the Outpatient department of the Clinic for Infectious and Tropical Diseases "Prof. Dr. Kosta Todorović" in Belgrade between August and November 2020 and diagnosed with COVID-19. Based on clinical criteria developed by the World Health Organization, patients were classified according to the severity of the disease into those with mild, moderate, and severe disease. Demographic data, comorbidities, symptoms, and signs of SARS-CoV-2 infection were collected from the patients. Physical examination with measurement of vital signs and chest X-ray were performed in every patient. Based on these findings and World Health Organization criteria, patients were classified into disease severity groups (mild, moderate, and severe disease). Peripheral blood samples were taken to measure levels of serum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), ferritin, fibrinogen, D-dimer, albumin, transferrin, iron, and other inflammatory parameters. The median values of acute-phase reactants (APRs) and other inflammatory parameters were compared between patients with different disease severity, hospitalized and non-hospitalized patients, and survivors and non-survivors. Receiver operator characteristic (ROC) curves and Area-under-curve (AUC) were used to analyze the classification characteristics of individual APRs for disease severity, hospitalization, and death. In contrast, univariate and multivariate logistic regression analysis was used to identify independent predictors of severe and moderately severe disease, hospitalization, and death. Results: In patients with severe disease, hospitalized patients, and non-survivors, significantly higher levels of SAA, CRP, IL-6, PCT, and significantly lower levels of transferrin, albumin, and iron were present. Patients with severe disease and who were hospitalized also had significantly higher levels of ferritin, fibrinogen, erythrocyte sedimentation rate, neutrophils, and lower levels of lymphocytes and eosinophils. ROC analysis, based on AUC, showed that SAA levels demonstrated satisfactory classification characteristics for disease severity (0.794) and mortality (0.732) and good classification characteristics for hospitalization (0.853). Multivariate logistic regression analysis showed that age was a significant independent predictor of moderate and severe COVID-19, hospitalization, and death among all patients but also in gender-specific groups. In all participants, SAA levels were identified as a significant independent predictor of moderate and severe COVID-19 and hospitalization, and for males and females, only for severe COVID-19 and hospitalization. For mortality, significant independent predictors were age, albumin levels, and platelet count. Conclusion: Determination of the levels of SAA, other APRs, and inflammatory parameters in ambulatory care patients can be of great significance for assessing the severity and prognosis of COVID-19.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectserumski amiloid A, reaktanti akutne faze, teški akutni respiratorni sindrom koronavirus 2, SARS-CoV-2, koronavirusna bolest 2019, COVID-19, ambulantni pacijenti, težina bolesti, smrtni ishodisr
dc.subjectserum amyloid A, acute-phase ractants, Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, Coronavirus disease 2019, COVID-19, abulatory care patients, illness severity, fatal outcomesen
dc.titleProcena značaja serumskog amiloida A i drugih reaktanata akutne faze kod SARS-CoV-2 Infekcije na težinu kliničke slike, hospitalizaciju i smrtni ishodsr
dc.title.alternativeSignificance assessment of serum amyloid A and other acute phase reactants during SARS-CoV-2 infection for severity of the clinical presentation, hospitalization, and deathen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/156211/Disertacija_14200.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/156212/Izvestaj_Komisije_14200.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_21847


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