Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection

Abstract

Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.

Figure 1

MOS 36-item Short Form Health Survey (SF-36) results for severe recovered respiratory syndrome patients 12 years after recovery.

Figure 2

Differential serum metabolic profiles between recovered SARS and healthy volunteers. (A) OPLS-DA score plot separating the recovered SARS and healthy volunteers (Control). (B) Heat map of significantly altered metabolites detected by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry.

Figure 3

Mapping of differential metabolites related to energy metabolism (A). Relative serum levels of differentially expressed free carnitine, acylcarnitines with long chains, and the ratio of carnitines (C16 + C18) to carnitine (B). Data shown as mean ± SEM. * < 0.05, ** < 0.01.

Figure 4

Mapping of differential metabolites related to arginine and proline metabolism. Data shown as mean ± SEM. * < 0.05, ** < 0.01.

Figure 5

Major pathways of phospholipid and neutral lipid synthesis. (A) Dashed lines show fatty acid rearrangement through the remodeling process. Correlation analysis of very low-density lipoprotein, phosphatidylinositol, lysophosphatidylinositol, and total triglycerides in (B) recovered SARS and (C) healthy volunteers (Control).

Figure 6

(A) Cluster analysis of differentially expressed lipids. (B) Fatty acids as a result of phosphatidylinositol remodeling in recovered SARS patients sensitive to phospholipase A2.