COVID-19 and serum amyloid A (SAA)

Biomarker studies of COVID-19 are ongoing for triage of critically ill patients and for evaluation of treatment. Studies have shown that biomarkers could help for management of patients, such as risk stratification of patients who can lead to cytokine storm. Especially, C-reactive protein (CRP), serum amyloid A (SAA), ferritin, D-dimer, interleukin 6 (IL-6), procalcitonin (PCT), fibrinogen, have been measured to evaluate the severity of COVID-19 in studies [*1, 2].

Acute phase response (APR) is a series of physiological changes that occur as a result of inflammation, infection, trauma, and other events [*3]. SAA is, the same as CRP, one of the acute phase proteins (APP) synthesized in the liver as a part of APR. The structure of SAA protein is apolipoprotein associated with HDL. Although SAA is almost undetectable levels in healthy individuals, the concentrations can increase as much as 1000-fold 24 hours after APR starts [*3].

• Viral infection
• CRP is a widely used biomarker that increases when inflammation occurs. CRP levels rises in bacterial infection but remains low in viral infection, whereas SAA is reported to increase in both bacterial and viral infection [*4, 5].
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• COVID-19 patients
• From recent studies, SAA in COVID-19 patients might support previous studies in viral infectious disease. Li et al. (2020) demonstrated that severe / critically severe patients had significantly higher SAA levels than mild / moderate patients, moreover, SAA levels consistently went down in patients who had better prognosis [*6].

A review by Tjendra et al. (2020) reviewed the remarkable increase of SAA as well as elevated IL-6 level were most frequently reported in severely and critically ill patients [*1]. Other research analyzes the ROC curve of SAA and IL-6 in COVID-19 patients. When the detection of SAA alone, the area under the ROC curve (AUC) was 0.865 (95% CI: 0.799‐0.931; P < .05) and when both SAA and IL-6 were measured, the AUC was 0.904 (95% CI: 0.851‐0.958; P < 0.05) [*7].

In the aspects of a research by Mo et al. (2020) indicates the diagnostic value of SAA, CRP and PCT to predict disease progression of COVID-19 [*8]. The ROC curve was respectively: SAA 0.9683; CRP 0.8089, PCT 0.07684.

LZ-SAA ‘Eiken’ is the unique LA-TIA reagent for general clinical chemistry analyzers. It has been used at common clinical laboratories in Japan for more than 20 years. In addition to infectious diseases [*4, 9], research of rheumatoid arthritis [*10, 11], renal cell carcinoma [*12], Kawasaki disease [*13] has been reported using LZ-SAA.

LZ-SAA is applicable to general clinical chemistry analyzers, and it can be familiar to laboratories.  Product information > *Currently research use only

1. Tjendra Y, Al Mana AF, Espejo AP, et al. Predicting Disease Severity and Outcome in COVID-19 Patients: A Review of Multiple Biomarkers. Arch Pathol Lab Med. 2020 Dec 1;144(12):1465-1474. 
2. Kermali M, Khalsa RK, Pillai K, Ismail Z, Harky A. The role of biomarkers in diagnosis of COVID-19 - A systematic review. Life Sci. 2020 Aug 1;254:117788.
3. Sack GH. Serum amyloid A – a review. Mol Med 24, 46 (2018).
4. Nakayama T, Sonoda S, Urano T, et al. Monitoring both serum amyloid protein A and C-reactive protein as inflammatory markers in infectious diseases. Clin Chem. 1993 Feb;39(2):293-7.
5. Yip TT, Chan JW, Cho WC, et al. Protein chip array profiling analysis in patients with severe acute respiratory syndrome identified serum amyloid a protein as a biomarker potentially useful in monitoring the extent of pneumonia. Clin Chem. 2005 Jan;51(1):47-55. 
6. Li H, Xiang X, Ren H, et al. Serum Amyloid A is a biomarker of severe Coronavirus Disease and poor prognosis. J Infect. 2020 Jun;80(6):646-655.
7. Liu Q, Dai Y, Feng M, et al. Associations between serum amyloid A, interleukin-6, and COVID-19: A cross-sectional study. J Clin Lab Anal. 2020 Oct;34(10):e23527. 
8. Mo XN, Su ZQ, Lei CL, et al. Serum amyloid A is a predictor for prognosis of COVID-19. Respirology. 2020 Jul;25(7):764-765. 
9. Miwata H, Yamada T, Okada M, et al. Serum amyloid A protein in acute viral infections. Arch Dis Child. 1993;68(2):210-214. 
10. Kokubun M, Imafuku Y, Okada M, et al. Serum amyloid A (SAA) concentration varies among rheumatoid arthritis patients estimated by SAA/CRP ratio. Clin Chim Acta. 2005 Oct;360(1-2):97-102. 
11. Yamada T, Okuda Y, Takasugi K, et al. Relative serum amyloid A (SAA) values: the influence of SAA1 genotypes and corticosteroid treatment in Japanese patients with rheumatoid arthritis. Ann Rheum Dis. 2001 Feb;60(2):124-7.
12. Kimura M, Tomita Y, Imai T, et al. Significance of serum amyloid A on the prognosis in patients with renal cell carcinoma. Cancer. 2001 Oct 15;92(8):2072-5.
13. Mitani Y, Sawada H, Hayakawa H, et al. Elevated levels of high-sensitivity C-reactive protein and serum amyloid-A late after Kawasaki disease: association between inflammation and late coronary sequelae in Kawasaki disease. Circulation. 2005 Jan 4;111(1):38-43.