이지영 (연세대학교)

이지영 (연세대학교)

문명희 (연세대학교)

이지영 (연세대학교)

박환규 (연세대학교)

성제경 (서울대학교 )

문명희 (연세대학교)

The emergence of SARS-CoV-2, the virus responsible for COVID-19, lately posed a significant threat to public health worldwide. COVID-19 is characterized by symptoms such as fatigue, coughing, chest tightness, shortness of breath, palpitations, muscle pain, and difficulty concentrating. These symptoms may be associated with various conditions, including organ damage, post-viral infection syndrome, post-critical care syndrome, and related conditions. Lipids serve as both a source of energy and essential components of cells, playing a crucial role in cellular signaling pathways and regulating cell membrane permeability. Therefore, investigating lipidomic alterations related to organ damage and recovery caused by metabolic changes after SARS-CoV-2 infection is of interest.

In this study, lung, liver, and serum samples from K18-hACE2 mice were examined. To compare lipid change patterns between mild and severe infection, two levels of infection were used: 1x10^2 PFU/mL and 1x10^5 PFU/mL injected into the nasal cavity. Lipid changes were observed at 1, 2, 5, 7, 10, and 14 days post-infection (dpi). Samples injected with 1x10^5 PFU/mL were observed up to 7 dpi due to mortality occurring after 7 days. Lipids were extracted using a modified Folch method with MTBE (Methyl-tert-butyl ether) and analyzed qualitatively and quantitatively using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization tandem mass spectrometry (nUHPLC-ESI-MS/MS).

The recovery process from COVID-19 infection was observed in the lung, liver, and serum of K18-hACE2 mice by monitoring changes in lipid composition using nUHPLC-ESI-MS/MS. Qualitative analysis identified a total of 698, 869, and 472 lipids in the lung, liver, and serum samples, respectively. With low-dose infection (1x10^2 PFU/mL), most lipid classes exhibited significant decreases in lung tissue at 2 dpi, followed by subsequent recovery. Similarly, with high-dose infection (1x10^5 PFU/mL), most lipid classes showed significant reductions in lung tissue at 1 dpi, followed by subsequent recovery. However, triacylglycerol (TG) exhibited a steady decreasing trend in lung tissue. Even in the liver, most lipid classes decreased and then recovered in late dpi. In serum, most lipid classes decrease significantly at 7 dpi. Both the lung and liver exhibited similar trends, where PI levels decreased at high doses and increased or returned to baseline at low doses. PC/PE ratio decreased at 7 dpi in the high-dose group and did not recover, whereas it did recover in the low-dose group. In serum, LPC levels showed minimal changes in saturated lipids, but a tendency to decrease in unsaturated lipids at high doses. LPI levels significantly increased in the high-dose group within saturated lipids, while showing a decreasing trend in the high-dose group within unsaturated lipids. Quantitative analysis was accomplished to assess the degree of recovery in mice infected with COVID-19. This study will contribute to understanding organ damage and recovery resulting from COVID-19 infection.