The utility of serum amyloid A and other acute-phase reactants determination in ambulatory care COVID-19 patients

Serum amyloid A in ambulatory care COVID-19 patients

  • Boris Jegorovic Clinic for Infectious and Tropical Diseases “Prof. dr Kosta Todorovic”, University Clinical Center of Serbia, Belgrade, Serbia
  • Aleksandra Nikolic Institute for Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Neda Milinkovic Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
  • Svetlana Ignjatovic Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
  • Sandra Sipetic Grujicic Institute for Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Keywords: serum amyloid A, SAA, COVID-19, SARS-CoV-2, ambulatory care, acute-phase reactants

Abstract


Background: The unpredictable course of Coronavirus Disease 19 (COVID-19) is making good severity assessment tools crucial. This study aimed to assess the usefulness of serum amyloid A (SAA) and other acute-phase reactants (APRs) in ambulatory COVID-19 patients and identified relationships between these markers and disease outcomes.

Methods: From August to November 2020, patients seen in the outpatient department of the Clinic for Infectious and Tropical Diseases (Belgrade, Serbia) with confirmed COVID-19 were included. Based on World Health Organization criteria, patients were classified into mild, moderate, and severe disease groups. SAA, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), ferritin, fibrinogen, D-dimer, albumin, and transferrin were measured. The Receiver operator characteristic (ROC) curve analysis was used for the classification characteristics assessment of individual APRs for the severity of illness, hospitalization, and survival. The median values of all APRs were compared between COVID-19 severity groups, hospitalized and non-hospitalized patients, and survivors and non-survivors.

Results: Higher levels of SAA, CRP, IL-6, PCT, and lower levels of transferrin and albumin were observed in severe cases, hospitalized patients, and non-survivors. Based on ROC curve analysis AUC for SAA has fair classification performance for disease severity (0.794) and death (0.732) and good performance for hospitalization (0.853).

Conclusion: SAA is a valuable marker in everyday practice for assessing COVID-19 severity and prognosis in ambulatory patients.

References


1.    Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727–33. Available from: https://doi.org/10.1056/NEJMoa2001017


2.    World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020. 2020 [cited 2022 Dec 30]. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020


3.    Zeng H, Ma Y, Zhou Z, Liu W, Huang P, Jiang M, et al. Spectrum and clinical characteristics of symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) with and without pneumonia. Front Med. 2021 Apr 1;8:645651.Available from: https://doi.org/10.3389/fmed.2021.645651


4.    García-González P, Tempio F, Fuentes C, Merino C, Vargas L, Simon V, et al. Dysregulated immune responses in COVID-19 patients correlating with disease severity and invasive oxygen requirements. Front Immunol. 2021;12:769059. Available from: https://doi.org/10.3389/fimmu.2021.769059


5.    Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J Mol Histol. 2020;51(6):613–28. Available from: https://doi.org/10.1007/s10735-020-09915-3


6.     Prabhala S, Sivakoti S, Sahoo B. Utility of acute-phase reactants testing in clinical practice. Indian J Community Fam Med. 2021 Jan 1;7(1):12. Available from: https://doi.org/10.4103/IJCFM.IJCFM_82_20


7.    Samprathi M, Jayashree M. Biomarkers in COVID-19: An up-to-date review. Front Pediatr. 2021;8:607647. Available from: https://doi.org/10.3389/fped.2020.607647


8.    Khalil RH, Al-Humadi N. Types of acute phase reactants and their importance in vaccination. Biomed Rep. 2020 Apr 12;12(4):143–52. Available from: https://doi.org/10.3892/br.2020.1276


9.    Sack GH. Serum amyloid A – a review. Mol Med. 2018 Aug 30;24(1):46. Available from: https://doi.org/10.1186/s10020-018-0047-0


10.   Yormaz B, Ergun D, Tulek B, Ergun R, Korez KM, Suerdem M, et al. The evaluation of prognostic value of acute phase reactants in the COVID-19. Bratisl Lek Listy. 2020;121(9):628–33. Available from: https://doi.org/10.4149/BLL_2020_103


11.   Sayit AT, Elmali M, Deveci A, Gedikli O. Relationship between acute phase reactants and prognosis in patients with or without COVID-19 pneumonia. Rev Inst Med Trop Sao Paulo. 2021 Jun 25;63:e51. Available from: https://doi.org/10.1590/S1678-9946202163051


12.   Cheng L, Yang JZ, Bai WH, Li ZY, Sun LF, Yan JJ, et al. Prognostic value of serum amyloid A in patients with COVID-19. Infection. 2020 Oct;48(5):715–22. Available from: https://doi.org/10.1007/s15010-020-01468-7


13.   Debi H, Itu ZT, Amin MT, Hussain F, Hossain MS. Association of serum C-reactive protein (CRP) and D-dimer concentration on the severity of COVID-19 cases with or without diabetes: a systematic review and meta-analysis. Expert Rev Endocrinol Metab. 2022 Jan 2;17(1):83–93. Available from: https://doi.org/10.1080/17446651.2022.2002146


14.   Para O, Caruso L, Pestelli G, Tangianu F, Carrara D, Maddaluni L, et al. Ferritin as prognostic marker in COVID-19: the FerVid study. Postgrad Med. 134(1):58–63. Available from: https://doi.org/10.1080/00325481.2021.1990091


15.   Aon M, Alsaeedi A, Alzafiri A, Ibrahim MM, Al-Shammari A, Al-Shammari O, et al. The association between admission procalcitonin level and the severity of COVID-19 pneumonia: a retrospective cohort study. Med Kaunas Lith. 2022 Oct 3;58(10):1389. Available from: https://doi.org/10.3390/medicina58101389


16.   Turcato G, Zaboli A, Kostic I, Melchioretto B, Ciccariello L, Zaccaria E, et al. Severity of SARS-CoV-2 infection and albumin levels recorded at the first emergency department evaluation: a multicentre retrospective observational study. Emerg Med J. 2022 Jan 1;39(1):63–9. Available from: https://doi.org/10.1136/emermed-2020-210081


17.   Claise C, Saleh J, Rezek M, Vaulont S, Peyssonnaux C, Edeas M. Low transferrin levels predict heightened inflammation in patients with COVID-19: New insights. Int J Infect Dis. 2022 Mar;116:74–9. Available from: https://doi.org/10.1016/j.ijid.2021.12.340


18.   Sabaka P, Koščálová A, Straka I, Hodosy J, Lipták R, Kmotorková B, et al. Role of interleukin 6 as a predictive factor for a severe course of COVID-19: Retrospective data analysis of patients from a long-term care facility during COVID-19 outbreak. BMC Infect Dis. 2021 Mar 29;21(1):308. Available from: https://doi.org/10.1186/s12879-021-05945-8


19.   Li H, Xiang X, Ren H, Xu L, Zhao L, Chen X, et al. Serum amyloid A is a biomarker of severe coronavirus disease and poor prognosis. J Infect. 2020 Jun;80(6):646–55.Available from: https://doi.org/10.1016/j.jinf.2020.03.035


20.   Chen M, Wu Y, Jia W, Yin M, Hu Z, Wang R, et al. The predictive value of serum amyloid A and C-reactive protein levels for the severity of coronavirus disease 2019. Am J Transl Res. 2020;12(8):4569–75. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476119/


21.   Liu Q, Dai Y, Feng M, Wang X, Liang W, Yang F. Associations between serum amyloid A, interleukin-6, and COVID-19: a cross-sectional study. J Clin Lab Anal. 2020 Oct;34(10):e23527. Available from: https://doi.org/10.1002/jcla.23527


22.   World Health Organisation. Clinical management of COVID-19 patients: living guideline, 23 November 2021. World Health Organization; 2021 [cited 2023 Jan 1]. Available from: https://apps.who.int/iris/bitstream/handle/10665/349321/WHO-2019-nCoV-clinical-2021.2-eng.pdf


23.   Arslan FD, Karakoyun I, Basok BI, Aksit MZ, Celik E, Dogan K, et al. The effects of education and training given to phlebotomists for reducing preanalytical errors. J Med Biochem. 2018 Apr 1;37(2):172–80. Available from: https://doi.org/10.1515/jomb-2017-0045


24.   Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020 Jul 16;20(1):519. Available from: https://doi.org/10.1186/s12879-020-05242-w


25.   Miwata H, Yamada T, Okada M, Kudo T, Kimura H, Morishima T. Serum amyloid A protein in acute viral infections. Arch Dis Child. 1993 Feb 1;68(2):210–4. Available from: https://doi.org/10.1136/adc.68.2.210


26.   Ahnach M, Zbiri S, Nejjari S, Ousti F, Elkettani C. C-reactive protein as an early predictor of COVID-19 severity. J Med Biochem. 2020 Oct 2;39(4):500–7.Available from: https://doi.org/10.5937/jomb0-27554


27.   Zhang H, Du F, Cao XJ, Feng XL, Zhang HP, Wu ZX, et al. Clinical characteristics of coronavirus disease 2019 (COVID-19) in patients out of Wuhan from China: a case control study. BMC Infect Dis. 2021 Feb 24;21(1):207. Available from: https://doi.org/10.1186/s12879-021-05897-z


28.   Velavan TP, Kuk S, Linh LTK, Lamsfus Calle C, Lalremruata A, Pallerla SR, et al. Longitudinal monitoring of laboratory markers characterizes hospitalized and ambulatory COVID-19 patients. Sci Rep. 2021 Jul 14;11(1):14471. Available from: https://doi.org/10.1038/s41598-021-93950-x


29.   Santa Cruz A, Mendes-Frias A, Oliveira AI, Dias L, Matos AR, Carvalho A, et al. Interleukin-6 is a biomarker for the development of fatal Severe Acute Respiratory Syndrome Coronavirus 2 pneumonia. Front Immunol. 2021 Feb 18;12:613422. Available from: https://doi.org/10.3389/fimmu.2021.613422


30.   Tong-Minh K, van der Does Y, Engelen S, de Jong E, Ramakers C, Gommers D, et al. High procalcitonin levels associated with increased intensive care unit admission and mortality in patients with a COVID-19 infection in the emergency department. BMC Infect Dis. 2022 Feb 21;22(1):165. Available from: https://doi.org/10.1186/s12879-022-07144-5


31.   Level C, Chauveau P, Delmas Y, Lasseur C, Pellé G, Peuchant E, et al. Procalcitonin: a new marker of inflammation in haemodialysis patients? Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2001 May;16(5):980–6. Available from: https://doi.org/10.1093/ndt/16.5.980


32.   Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chim Acta Int J Clin Chem. 2020 Jun;505:190–1. Available from: https://doi.org/10.1016/j.cca.2020.03.004


33.   Banchini F, Cattaneo GM, Capelli P. Serum ferritin levels in inflammation: a retrospective comparative analysis between COVID-19 and emergency surgical non-COVID-19 patients. World J Emerg Surg. 2021 Mar 8;16(1):9. Available from: https://doi.org/10.1186/s13017-021-00354-3


34.   Lino K, Guimarães GMC, Alves LS, Oliveira AC, Faustino R, Fernandes CS, et al. Serum ferritin at admission in hospitalized COVID-19 patients as a predictor of mortality. Braz J Infect Dis. 2021 Mar 15;25(2):101569. Available from: https://doi.org/10.1016/j.bjid.2021.101569


35.   Carubbi F, Salvati L, Alunno A, Maggi F, Borghi E, Mariani R, et al. Ferritin is associated with the severity of lung involvement but not with worse prognosis in patients with COVID-19: data from two Italian COVID-19 units. Sci Rep. 2021 Mar 1;11:4863. Available from: https://doi.org/10.1038/s41598-021-83831-8


36.   Abdelhakam DA, Badr FM, Abd El Monem Teama M, Bahig Elmihi NM, El-Mohamdy MA. Serum amyloid A, ferritin and carcinoembryonic antigen as biomarkers of severity in patients with COVID-19. Biomed Rep. 2022 Feb;16(2):13. Available from: https://doi.org/10.3892/br.2021.1496


37.   Liu SL, Wang SY, Sun YF, Jia QY, Yang CL, Cai PJ, et al. Expressions of SAA, CRP, and FERR in different severities of COVID-19. Eur Rev Med Pharmacol Sci. 2020 Nov;24(21):11386–94. Available from: https://doi.org/10.26355/eurrev_202011_23631


38.   Sui J, Noubouossie DF, Gandotra S, Cao L. Elevated plasma fibrinogen is associated with excessive inflammation and disease severity in COVID-19 patients. Front Cell Infect Microbiol. 2021 Aug 3;11:734005. Available from: https://doi.org/10.3389/fcimb.2021.734005


39.   Long W, Yang J, Li Z, Li J, Chen S, Chen D, et al. Abnormal fibrinogen level as a prognostic indicator in coronavirus disease patients: a retrospective cohort study. Front Med. 2021 Jun 14;8:687220. Available from: https://doi.org/10.3389/fmed.2021.687220


40.   Thachil J. The protective rather than prothrombotic fibrinogen in COVID‐19 and other inflammatory states. J Thromb Haemost. 2020 Aug;18(8):1849–52. Available from: https://doi.org/10.1111/jth.14942


41.   Conway EM, Mackman N, Warren RQ, Wolberg AS, Mosnier LO, Campbell RA, et al. Understanding COVID-19-associated coagulopathy. Nat Rev Immunol. 2022 Oct;22(10):639–49. Available from: https://doi.org/10.1038/s41577-022-00762-9


42.   Kheir M, Saleem F, Wang C, Mann A, Chua J. Higher albumin levels on admission predict better prognosis in patients with confirmed COVID-19. PLoS ONE. 2021 Mar 16;16(3):e0248358. Available from: https://doi.org/10.1371/journal.pone.0248358


43.   Acharya R, Poudel D, Bowers R, Patel A, Schultz E, Bourgeois M, et al. Low Serum Albumin Predicts Severe Outcomes in COVID-19 Infection: A Single-Center Retrospective Case-Control Study. J Clin Med Res. 2021 May;13(5):258–67. Available from: https://doi.org/10.14740/jocmr4507


44.   Huang J, Cheng A, Kumar R, Fang Y, Chen G, Zhu Y, et al. Hypoalbuminemia predicts the outcome of COVID‐19 independent of age and comorbidity. J Med Virol. 2020 Oct;92(10):2152–8. Available from: https://doi.org/10.1002/jmv.26003


45.   Zhang L, Yu W, Zhao Y, Chen X, Wang P, Fan X, et al. Albumin Infusion May Improve the Prognosis of Critical COVID-19 Patients with Hypoalbuminemia in the Intensive Care Unit: A Retrospective Cohort Study. Infect Drug Resist. 2022 Oct 19;15:6039–50. Available from: https://doi.org/10.2147/IDR.S383818


46.   Yadav D, Pvsn KK, Tomo S, Sankanagoudar S, Charan J, Purohit A, et al. Association of iron-related biomarkers with severity and mortality in COVID-19 patients. J Trace Elem Med Biol Organ Soc Miner Trace Elem GMS. 2022 Dec;74:127075. Available from: https://doi.org/10.1016/j.jtemb.2022.127075


47.   Shah A, Frost JN, Aaron L, Donovan K, Drakesmith H, Collaborators. Systemic hypoferremia and severity of hypoxemic respiratory failure in COVID-19. Crit Care Lond Engl. 2020 Jun 9;24(1):320. Available from: https://doi.org/10.1186/s13054-020-03051-w


 

Published
2023/03/19
Section
Original paper