Procena značaja serumskog amiloida A i drugih reaktanata akutne faze kod SARS-CoV-2 Infekcije na težinu kliničke slike, hospitalizaciju i smrtni ishod
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
Докторанд
Jegorović, BorisМентор
Šipetić-Grujičić, SandraЧланови комисије
Ignjatović, SvetlanaMaksimović, Jadranka
Stevanović, Goran
Bećarević, Mirjana
Метаподаци
Приказ свих података о дисертацијиСажетак
Krajem 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 para...metara 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.
Introduction: 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 patien...ts 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.