Serum Amyloid A Levels Linked to Likelihood of Developing Severe COVID-19

Results of research papers published during the current pandemic suggest that increased levels of the blood biomarker serum amyloid A predict development of severe or fatal forms of COVID-19.

Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of inflammation. A-SAA genes and proteins are significantly activated during the acute phase response, which comprises a number of phenomena that occur in the presence of inflammation and infection, e.g., increased temperature and hormonal and metabolic alterations.

Circulating SAA concentrations, typically low under physiological circumstances, can increase up to 1000-fold within the first 24 to 48 hours of an acute phase response. This is the consequence of increased synthesis in the liver that is triggered by several stimuli, including tumor necrosis factor (TNF), interleukin (IL)-1beta, IL-6, and interferon gamma (IFN-gamma). SAA, in turn, can activate the complement system and further increase the synthesis of TNF, IL-1beta, and IL-6, and activate other proinflammatory cytokines such as IL-1alpha and IL-23.

Two systematic reviews and meta-analyses on a relatively limited number of studies, had reported a significant and positive association between SAA concentrations and COVID-19 severity. Thus, it was plausible that the acute increase in SAA concentrations in patients with COVID-19 might not only reflect the presence of an acute phase response, but also herald the development of a cytokine storm and, consequently, multi-organ failure and an increased risk of adverse outcomes.

In this light, investigators at Flinders University (Adelaide, Australia) and the University of Sassari (Italy) analyzed results from nineteen published studies involving 5617 COVID-19 patients to determine if a link could be demonstrated between SAA levels and COVID-19.

The investigators reported that pooled results indicated that SAA concentrations were significantly higher in patients with severe disease and non-survivors than in patients with mild disease or controls. SAA concentrations were significantly and positively associated with higher COVID-19 severity and mortality.

"Our analyses showed that COVID-19 patients with severe disease or who eventually died had significantly higher levels of SAA when compared to patients with mild COVID-19," said senior author Dr. Arduino Mangon, professor of clinical pharmacology at Flinders University. Patients with severe forms of coronavirus disease 2019 have excessive inflammation, alterations in clot formation, and significant damage in several organs, particularly the lung, the kidney, the heart, and the liver. This chemical [SAA] may help, together with other patient characteristics, in predicting which COVID-19 patients are likely to deteriorate and require aggressive management."

The serum amyloid A study was published in the March 15, 2021, online edition of the International Journal of Infectious Diseases.

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Flinders University
University of Sassari